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

Sponsors and Collaborators:	Southwest Oncology Group 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 4 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	Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: filgrastim Drug: paclitaxel Drug: pegfilgrastim Drug: trastuzumab	Phase III

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Mammography

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Filgrastim Paclitaxel Pegfilgrastim Trastuzumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

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 4 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 4 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 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 [ 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:	4500
Study Start Date:	November 2003
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator 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.	Drug: cyclophosphamide Given IV or orally Drug: doxorubicin hydrochloride Given IV or orally Drug: filgrastim Given subcutaneously Drug: paclitaxel Given IV or orally Drug: pegfilgrastim Given subcutaneously Drug: trastuzumab Given IV
Arm II: Experimental 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.	Drug: cyclophosphamide Given IV or orally Drug: doxorubicin hydrochloride Given IV or orally Drug: filgrastim Given subcutaneously Drug: paclitaxel Given IV or orally Drug: pegfilgrastim Given subcutaneously Drug: trastuzumab Given IV
Arm III: Active Comparator 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.	Drug: cyclophosphamide Given IV or orally Drug: doxorubicin hydrochloride Given IV or orally Drug: filgrastim Given subcutaneously Drug: paclitaxel Given IV or orally Drug: pegfilgrastim Given subcutaneously Drug: trastuzumab Given IV
Arm IV: Experimental 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.	Drug: cyclophosphamide Given IV or orally Drug: doxorubicin hydrochloride Given IV or orally Drug: filgrastim Given subcutaneously Drug: paclitaxel Given IV or orally Drug: trastuzumab Given IV

Detailed Description:

OBJECTIVES:

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.
Compare the overall survival of patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.
Correlate outcome with putative prognostic markers in patients treated with these regimens.

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.

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

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 464 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

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

More 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

Study ID Numbers:	CDR0000334899, SWOG-S0221
Study First Received:	October 3, 2003
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00070564
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIC breast cancer
male breast cancer

Study placed in the following topic categories:

Skin Diseases
Breast Neoplasms, Male
Paclitaxel
Trastuzumab

Breast Neoplasms
Cyclophosphamide
Doxorubicin
Breast Diseases

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Antimitotic Agents
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009