Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed Not specified NCI NSABP-B-38 NSABP-B-38, NCT00093795

Special Category: CTSU trial

Objectives

Primary

1. Compare disease-free survival in women with node-positive breast cancer treated with 3 different adjuvant chemotherapy regimens comprising dose-dense doxorubicin, cyclophosphamide, paclitaxel, and gemcitabine vs docetaxel, doxorubicin, and cyclophosphamide vs dose-dense doxorubicin, cyclophosphamide, and paclitaxel.

Secondary

1. Compare overall survival, recurrence-free interval, and distant recurrence-free interval, in patients treated with these regimens.
2. Compare the toxic effects of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed invasive breast cancer, meeting all of the following staging criteria:
  • Primary tumor T1-3 by clinical and pathological evaluation
  • Ipsilateral lymph nodes cN0, cN1, or cN2a by clinical evaluation
  • Ipsilateral lymph nodes pN1 (pN1mi, pN1a, pN1b, or pN1c), pN2a, pN3a, or pN3b* by pathologic evaluation
    • Must have completed 1 of the following procedures for evaluation of pathological nodal status:
      • Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes
      • Sentinel lymphadenectomy alone allowed provided 1 of the following criteria is met:
        • Pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1b
        • No additional non-sentinel lymph nodes are removed
      • Axillary lymphadenectomy without sentinel lymph node isolation procedure

   [Note: *Only if due to microscopic involvement of internal mammary node detected by sentinel lymph node dissection AND has > 3 positive axillary lymph nodes]




• Must have undergone prior lumpectomy or total mastectomy
  • Lumpectomy patients:
    • Surgical margins must be histologically free of invasive tumor AND ductal carcinoma in situ (DCIS) (lobular carcinoma in situ [LCIS] allowed)
      • Additional operative procedures may be performed to obtain clear margins* even if axillary evaluation has been completed
    • No diffuse tumors* by mammography
    • No other clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast unless proven to be histologically benign OR if malignant, surgically removed with clear margins
    • Planned whole breast irradiation required

     [Note: *Patients with persistent positive margins or diffuse tumors must undergo total mastectomy to be eligible for this study]




• No more than 84 days since last surgery for breast cancer staging or treatment



• No clinical or radiologic evidence of metastatic disease



• No contralateral breast cancer (invasive breast cancer or DCIS)



• No mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy evidence that the mass is not malignant



• No suspicious nodes in the contralateral axilla or suspicious supraclavicular nodes unless there is biopsy evidence of no tumor involvement



• No prior breast cancer, including DCIS
  • LCIS allowed



• Hormone receptor status:
  • Estrogen receptor (ER) status known
  • Progesterone receptor status known only if ER-negative

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for current breast cancer
• No prior anthracycline or taxane therapy for any malignancy

Endocrine therapy

• See Disease Characteristics
• Prior hormonal therapy for breast cancer allowed provided the duration of therapy was ≤ 28 days and it was administered before study entry
• No concurrent sex hormonal therapy (e.g., birth control pills, ovarian hormone replacement therapy, or Femring®)
  • Concurrent Vagifem® or Estring® for the management of vaginal or urinary symptoms allowed
• No concurrent raloxifene, tamoxifen, or other selective estrogen-receptor modulators (SERMs) for osteoporosis or breast cancer prevention

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy for current breast cancer
• No concurrent partial breast irradiation (lumpectomy patients)
• Concurrent irradiation of regional lymph nodes allowed provided plans are declared prior to study entry

Surgery

• See Disease Characteristics

Other

• Concurrent calcium supplements, cholecalciferol (vitamin D), calcitonin (e.g., Miacalcin®), or bisphosphonates (e.g., Actonel® or Fosamax®) for the management of osteoporosis allowed
• No other concurrent investigational agents for the treatment of breast cancer

Patient Characteristics:

Age

• Not specified

Sex

• Female

Menopausal status

• Not specified

Performance status

• Zubrod 0-1

Life expectancy

• At least 10 years

Hematopoietic

• Absolute granulocyte count ≥ 1,200/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin ≤ upper limit of normal (ULN)* (1.5 times ULN if due to Gilbert's disease or similar syndrome)
• Alkaline phosphatase ≤ 2.5 times ULN*
• AST ≤ 1.5 times ULN*
• No hepatic disease that would preclude study participation

 [Note: *Bilirubin, AST, OR alkaline phosphatase > ULN allowed provided no metastatic liver disease is present on imaging]

Renal

• Postoperative creatinine ≤ ULN
• No renal disease that would preclude study participation

Cardiovascular

• LVEF ≥ lower limit of normal by echocardiogram or MUGA
• No cardiac disease that would preclude the use of anthracyclines, including any of the following:
  • History of myocardial infarction documented by elevated cardiac enzymes or regional wall abnormalities
  • Angina pectoris requiring anti-anginal medication
  • Documented history of congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Severe conduction abnormality
  • Valvular disease with documented cardiac function compromise
  • Uncontrolled hypertension, defined as blood pressure > 160/100 mm Hg with antihypertensive therapy
• No other cardiovascular disease that would preclude study participation

Other

• Not pregnant or nursing
• Fertile patients must use effective non-hormonal contraception
• No other malignancy within the past 5 years except treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, melanoma in situ, or carcinoma in situ of the colon
  • Considered to be low-risk for recurrence
• No condition that would preclude corticosteroid administration
• No sensory or motor neuropathy ≥ grade 2
• No other nonmalignant systemic disease that would preclude study participation
• No psychiatric or addictive disorder or other condition that would preclude study participation

Expected Enrollment

A total of 4,800 patients will be accrued for this study within 4 years.

Outcomes

Disease-free survival every 6 months for 5 years and then annually thereafter

Survival every 6 months for 5 years and then annually thereafter
Recurrence-free interval every 6 months for 5 years and then annually thereafter
Distant recurrence-free interval every 6 months for 5 years and then annually thereafter
Toxicity as assessed by adverse events after each course and 3 months after completion of study treatment

Outline

This is a randomized, multicenter study. Patients are stratified according to number of positive lymph nodes (1-3 vs 4-9 vs ≥ 10), hormone receptor status (estrogen receptor [ER]- and progesterone receptor [PgR]- negative vs ER- and/or PgR-positive), type of prior surgery and planned radiotherapy (lumpectomy and local radiotherapy [RT] without regional RT vs lumpectomy and local RT with regional RT vs mastectomy without RT vs mastectomy with local and/or regional RT). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses.



• Arm II: Patients receive AC chemotherapy comprising doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 14 days for 4 courses. Beginning 14 days after the last dose of AC, patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses.



• Arm III: Patients receive AC chemotherapy as in arm II. Beginning 14 days after the last dose of AC, patients receive paclitaxel as in arm II and gemcitabine IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 4 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-12 weeks after the last dose of chemotherapy, patients with ER-positive and/or PgR-positive tumors receive hormonal therapy.

Beginning no sooner than 3 weeks after the last course of chemotherapy, patients treated with lumpectomy undergo whole-breast radiotherapy. Patients treated with mastectomy may undergo chest wall and/or regional nodal radiotherapy.

Patients are followed every 6 months for 5 years and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Sandra Swain, MD, Protocol chair		Ph: 202-877-8112

Related Information

PDQ® clinical trial ACOSOG-Z0011

Registry Information
Official Title		A Phase III, Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Node-Positive Breast Cancer: Docetaxel/Doxorubicin/Cyclophosphamide (TAC); Dose-Dense (DD) Doxorubicin/Cyclophosphamide Followed By DD Paclitaxel (DD AC→P); DD AC Followed By DD Paclitaxel Plus Gemcitabine (DD AC→PG)
Trial Start Date		2004-10-01
Registered in ClinicalTrials.gov		NCT00093795
Date Submitted to PDQ		2004-08-30
Information Last Verified		2008-09-08
NCI Grant/Contract Number		CA12027

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