Combination Chemotherapy in Treating Women With Stage II or Stage IIIA Breast Cancer That Has Spread to the Lymph Nodes

Breast Cancer Clinical Trial

Official title:

A Phase III Study of Doxorubicin-Cyclophosphamide Therapy Followed by Paclitaxel or Docetaxel Given Weekly or Every 3 Weeks in Patients With Axillary Node-Positive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004125
• Other study ID #: CDR0000067353
• Secondary ID: E1199CLB-49906NC
• Status: Completed
• Phase: Phase 3
• Start date: November 16, 1999
• Est. completion date: November 2016

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which regimen of chemotherapy is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of combination chemotherapy in treating women who have stage II or stage IIIA breast cancer that has spread to the lymph nodes.

Description:

OBJECTIVES:

• Compare the disease-free survival and overall survival in patients with node-positive or high-risk node-negative operable stage II or IIIA breast cancer treated with docetaxel or paclitaxel after doxorubicin and cyclophosphamide.

• Determine whether the weekly administration of paclitaxel or docetaxel for 12 weeks improves disease-free survival and overall survival when compared with the conventional schedule of every 3 weeks for 4 courses after doxorubicin and cyclophosphamide in this patient population.

• Compare the toxic effects of docetaxel and paclitaxel when administered weekly for 12 weeks versus every 3 weeks for 4 courses in these patients.

• Compare the toxicity of paclitaxel administered every 3 weeks for 4 courses or weekly for 12 weeks to that of docetaxel administered on the same schedules in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative vs unknown), nodal status (0 positive nodes vs 1-3 positive nodes vs 4-9 positive nodes vs at least 10 positive nodes), tumor size (no more than 5 cm vs more than 5 cm vs unknown), and type of prior surgery (mastectomy vs breast conservation surgery). Patients are randomized to one of four treatment arms.

• Arm I: Patients receive doxorubicin IV and cyclophosphamide IV every 3 weeks for 4 courses (weeks 1-12). Beginning at week 13, patients receive paclitaxel IV over 3 hours every 3 weeks for 4 courses.

• Arm II: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive paclitaxel IV over 1 hour weekly for 12 weeks.

• Arm III: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour every 3 weeks for 4 courses.

• Arm IV: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour weekly for 12 weeks.

Within 4 weeks after completion of chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen daily for 5 years.

After completion of all chemotherapy, patients with prior segmental mastectomy receive radiotherapy once daily 5 days per week for 5-6 weeks. Patients with prior modified radical mastectomy may receive radiotherapy after chemotherapy completion at the investigator's discretion.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 5,000 patients will be accrued for this study within 1.27 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: November 2016
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed operable stage IIA, IIB, or IIIA adenocarcinoma of the breast with histologically involved lymph nodes (T1, 2, or 3; N1 or 2; M0) OR high-risk node-negative disease (T2 or 3; N0)

• Primary tumor at least 2.1 cm in diameter for node-negative disease

• Bilateral breast disease allowed if at least 1 primary tumor meets the criteria above

• Must have had at least 6 axillary lymph nodes removed at dissection and at least one node positive for metastasis OR

• Sentinel node biopsy negative for metastasis (sentinel node biopsy positive allowed if enrolled on American College of Surgery Trial Z0011 and have beenrandomized to receive no axillary dissection)

• Additional axillary nodes may be obtained provided they are also negative for metastasis

• Complete tumor removal by either a modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy

• Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed)

• Concurrent enrollment on American College of Surgery Trial Z0010, Z0011, or NSABP B-32 allowed

• Hormone receptor status:

• Estrogen receptor status positive, negative, or unknown

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

• SGOT no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No history of myocardial infarction

• No congestive heart failure

• No significant ischemic or valvular heart disease

Other:

• No other prior invasive malignancies within the past 5 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the cervix

• No hypersensitivity to paclitaxel or docetaxel or other similarly formulated drugs (with Cremophor or polysorbate)

• Not pregnant or nursing

• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for breast cancer

Endocrine therapy:

• Prior tamoxifen of no more than 4 weeks duration for breast cancer allowed

• Prior tamoxifen or other selective estrogen receptor modulator (SERM) for chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (e.g., osteoporosis) allowed

• No concurrent tamoxifen or other SERMs

Radiotherapy:

• No prior radiotherapy for this malignancy

• At least 2 weeks since prior radiotherapy to the breast for ductal carcinoma in situ

Surgery:

• See Disease Characteristics

• Less than 84 days since prior surgical procedure to adequately treat primary tumor

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide

• docetaxel

• doxorubicin hydrochloride

• paclitaxel

• tamoxifen citrate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa
United States	University of California San Diego Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Schneider Children's Hospital at North Shore	Manhasset	New York
United States	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee
United States	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Rhode Island Hospital	Providence	Rhode Island
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Veterans Affairs Medical Center - Togus	Togus	Maine
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	Cancer and Leukemia Group B, National Cancer Institute (NCI), North Central Cancer Treatment Group, SWOG Cancer Research Network

Country where clinical trial is conducted

United States, 

References & Publications (2)

Sparano JA, Wang M, Martino S, et al.: Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer: results of North Ame

Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. doi: 10.1056/NEJMoa0707056. Erratum In: N E — View Citation