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

NCT ID: NCT00004125

Last Updated: 2023-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

1999-11-16

Study Completion Date

2016-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Breast Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

cyclophosphamide

Intervention Type DRUG

docetaxel

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

paclitaxel

Intervention Type DRUG

tamoxifen citrate

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Eastern Cooperative Oncology Group

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Joseph A. Sparano, MD

Role: STUDY_CHAIR

Albert Einstein College of Medicine

Edith A. Perez, MD

Role: STUDY_CHAIR

Mayo Clinic

Silvana Martino, DO

Role: STUDY_CHAIR

Saint John's Cancer Institute

Vicky E. Jones, MD

Role: STUDY_CHAIR

University of California, San Diego

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Site Status

Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, United States

Site Status

Holden Comprehensive Cancer Center at The University of Iowa

Iowa City, Iowa, United States

Site Status

Veterans Affairs Medical Center - Togus

Togus, Maine, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

Schneider Children's Hospital at North Shore

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, United States

Site Status

Green Mountain Oncology Group

Bennington, Vermont, United States

Site Status

Vermont Cancer Center

Burlington, Vermont, United States

Site Status

Veterans Affairs Medical Center - White River Junction

White River Junction, Vermont, United States

Site Status

Veterans Affairs Medical Center - Richmond

Richmond, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type RESULT
PMID: 18420499 (View on PubMed)

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 American Breast Cancer Intergroup Trial E1199. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-48, 2005.

Reference Type RESULT

Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer. J Clin Oncol. 2015 Jul 20;33(21):2353-60. doi: 10.1200/JCO.2015.60.9271. Epub 2015 Jun 15.

Reference Type DERIVED
PMID: 26077235 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

E1199

Identifier Type: -

Identifier Source: secondary_id

CLB-49906

Identifier Type: -

Identifier Source: secondary_id

NCCTG-E1199

Identifier Type: -

Identifier Source: secondary_id

SWOG-E1199

Identifier Type: -

Identifier Source: secondary_id

CDR0000067353

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Docetaxel in Breast Cancer
NCT00312208 COMPLETED PHASE3