Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer - Full Text View

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070564

Purpose

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating resected breast cancer.

PURPOSE: This randomized phase III trial is comparing 2 different regimens of combination chemotherapy to see how well they work in treating patients who have undergone surgery for stage I, stage II, or stage III breast cancer.

Condition	Intervention	Phase
Breast Cancer	Biological: pegfilgrastim Drug: AC regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Mammography

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Paclitaxel Pegfilgrastim

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 [ Designated as safety issue: No ]
Compare overall survival of patients among the 2 treatment arms by medical history and physical exam every 6 months for 5 years and then annually [ Designated as safety issue: No ]
Compare toxicity among the 2 treatment arms by medical history and physical exam every 6 months for 5 years and then annually [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Compare disease-free survival of patients among the 2 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 [ Designated as safety issue: No ]
Compare prognostic biomarkers with outcome and the interaction of these markers with treatment as measured by gene expression analysis before study entry [ Designated as safety issue: No ]

Estimated Enrollment:	3250
Study Start Date:	November 2003
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I (closed 11/10/10) 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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm II (closed 11/10/10) 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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Active Comparator: Arm III (closed 11/10/10) 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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm IV (closed 11/10/10) 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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm V Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm VI Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim as in arm V. 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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070564

Show 542 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Investigator:	George Thomas Budd, MD	The Cleveland Clinic
Investigator:	Halle C.F. Moore, MD	The Cleveland Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

Sucheston LE, Zhao H, Yao S, Zirpoli G, Liu S, Barlow WE, Moore HC, Thomas Budd G, Hershman DL, Davis W, Ciupak GL, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Livingston RB, Albain KS, Hayes DF, Ambrosone CB. Genetic predictors of taxane-induced neurotoxicity in a SWOG phase III intergroup adjuvant breast cancer treatment trial (S0221). Breast Cancer Res Treat. 2011 Jul 16; [Epub ahead of print]

Ambrosone CB, Sucheston LE, Zhao H, et al.: Variants in the BRCA1/Fanconi-anemia repair pathway and taxane-induced neuropathy in SWOG S0221. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-2001, 2009.

Responsible Party:	Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00070564 History of Changes
Other Study ID Numbers:	CDR0000334899, SWOG-S0221
Study First Received:	October 3, 2003
Last Updated:	January 17, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II breast cancer
stage IA breast cancer
stage IB breast cancer
stage IIIC breast cancer
male breast cancer

HER2-positive breast cancer
estrogen receptor-negative breast cancer
estrogen receptor-positive breast cancer
progesterone receptor-negative breast cancer
progesterone receptor-positive breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Doxorubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 09, 2012