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S0221 Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00070564
Recruitment Status : Active, not recruiting
First Posted : October 7, 2003
Results First Posted : April 17, 2017
Last Update Posted : April 15, 2024
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
SWOG Cancer Research Network

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Breast Cancer Biological: pegfilgrastim Drug: AC regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3294 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : November 2003
Actual Primary Completion Date : January 2015
Estimated Study Completion Date : January 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Disease-free Survival [ Time Frame: every 6 months (annually for mammograms) for 5 years ]
    Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.

  2. Overall Survival [ Time Frame: Every 6 months for 5 years ]
    Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.


Secondary Outcome Measures :
  1. Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [ Time Frame: Toxicity assessment was evaluated every 4 weeks while on protocol therapy. ]
    Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

  2. Disease-free Survival Comparison Between 2 Treatments in HR-positive, HER-2 Negative Group [ Time Frame: Biomarkers were measured by gene expression analysis before study entry. DFS were measured every 6 months for 5 years ]
    Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.

  3. Overall Survival Comparison Between 2 Treatments in HR-positive, HER-2 Negative Group [ Time Frame: Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years ]
    Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.

  4. Disease-free Survival Comparison Between 2 Treatments in HR-negative, HER-2 Negative Group [ Time Frame: Biomarkers were measured by gene expression analysis before study entry. DFS was measured every 6 months for 5 years ]
    Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.

  5. Overall Survival Comparison Between 2 Treatments in HR-negative, HER-2 Negative Group [ Time Frame: Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years ]
    Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.

  6. Disease-free Survival Comparison Between 2 Treatments in HER2-positive Group [ Time Frame: Biomarkers were measured by gene expression analysis before study entry. DFS was measured every 6 months for 5 years ]
    Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.

  7. Overall Survival Comparison Between 2 Treatments in HER-2 Positive Group. [ Time Frame: Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years ]
    Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00070564


Locations
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Sponsors and Collaborators
SWOG Cancer Research Network
National Cancer Institute (NCI)
Investigators
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Study Chair: George Thomas Budd, MD The Cleveland Clinic
Study Director: Halle C Moore, MD The Cleveland Clinic
More Information
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Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Publications of Results:
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.

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Responsible Party: SWOG Cancer Research Network
ClinicalTrials.gov Identifier: NCT00070564    
Other Study ID Numbers: CDR0000334899
S0221 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
First Posted: October 7, 2003    Key Record Dates
Results First Posted: April 17, 2017
Last Update Posted: April 15, 2024
Last Verified: April 2024
Keywords provided by SWOG Cancer Research Network:
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:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
 Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors