Docetaxel and Cyclophosphamide Compared to Anthracycline-Based Chemotherapy in Treating Women With HER2-Negative Breast Cancer

Not Recruiting

Trial ID: NCT01547741


RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of breast cancer cells, either by killing the cells or by stopping them from dividing. Giving the drugs in different combinations may kill more breast cancer cells. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating women with non-metastatic breast cancer.

Official Title

A Phase III Clinical Trial Comparing the Combination of Docetaxel Plus Cyclophosphamide to Anthracycline-Based Chemotherapy Regimens for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer

Stanford Investigator(s)

Irene Wapnir, MD
Irene Wapnir, MD

Professor of Surgery (General Surgery)


Inclusion Criteria:

   - The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
   of 0 or 1.

   - The tumor must be unilateral invasive adenocarcinoma of the breast on histologic

   - The breast cancer must be Human Epidermal Growth Factor Receptor 2 (HER2)-negative
   based on current American Society of Clinical Oncology (ASCO)/CAP Guideline
   Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer.
   If the result of the in situ hybridization testing (FISH, chromagen in situ
   hybridization [CISH], or other) is equivocal, the patient is eligible if there is no
   plan to administer HER2-targeted therapy.

   - All of the following staging criteria must be met according to American Joint
   Committee on Cancer (AJCC) criteria:

      - By pathologic evaluation, primary tumor must be pT1-3;

      - By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b,
      pN1c), pN2a, pN3a, or pN3b.

      - If pN0, at least one of the following criteria must be met:

      - ER negative and PgR negative; or

      - Pathologic tumor size greater than 2.0 cm; or

      - T1c (pathologic tumor size greater than 1.0 cm but less than or equal to 2.0 cm)
      and ER positive (PgR status may be positive or negative) and either grade 3
      histology or Oncotype DX® Recurrence Score of greater than or equal to 25.

   - Patients must have undergone either a total mastectomy or breast-conserving surgery

   - For patients who undergo lumpectomy, the margins of the resected specimen must be
   histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as
   determined by the local pathologist. If pathologic examination demonstrates tumor at
   the line of resection, additional operative procedures must be performed to obtain
   clear margins. If tumor is still present at the resected margin after re-excision(s),
   the patient must undergo total mastectomy to be eligible. (Patients with margins
   positive for lobular carcinoma in situ [LCIS] are eligible without additional

   - For patients who undergo mastectomy, margins must be histologically free of invasive
   tumor and DCIS.

   - Patients must have completed one of the following procedures for evaluation of
   pathologic nodal status:

      - Sentinel lymphadenectomy alone if pathologic nodal staging based on sentinel
      lymphadenectomy is pN0, pN1mi, or pN1b;

      - Sentinel lymphadenectomy alone if pathologic nodal staging based on sentinel
      lymphadenectomy is pN1a limited to 1 or 2 positive nodes and primary tumor is T1
      or T2 by pathologic evaluation;

      - Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph
      nodes if the sentinel node (SN) is positive; or

      - Axillary lymphadenectomy with or without SN isolation procedure.

   - The interval between the last surgery for breast cancer (treatment or staging) and
   randomization must be no more than 84 days.

   - Patients must have ER analysis performed on the primary tumor prior to randomization.
   Breast cancer must be assessed for ER status by current ASCO/CAP Guideline
   Recommendations for hormone receptor testing. If negative for ER, assessment of PgR
   must also be performed according to current ASCO/CAP Guideline Recommendations for
   hormone receptor testing. (Either a core biopsy or surgical resection specimen can be
   used for ER/PgR testing.)

   - The most recent postoperative blood counts, performed within 6 weeks prior to
   randomization, must meet the following criteria:

      - absolute neutrophil count (ANC) must be greater than or equal to 1200/mm3;

      - platelet count must be greater than or equal to 100,000/mm3; and

      - hemoglobin must be greater than or equal to 10 g/dL.

   - The following criteria for evidence of adequate hepatic function must be met based on
   the results of the most recent postoperative tests performed within 6 weeks prior to

      - total bilirubin must be less than or equal to upper limit of normal (ULN) for the
      lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN
      due to Gilbert's disease or similar syndrome involving slow conjugation of
      bilirubin; and

      - alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and

      - aspartate transaminase (AST) must be less than or equal to 1.5 x ULN for the lab.

      - Alkaline phosphatase and AST may not both be greater than the ULN. For example,
      if the alkaline phosphatase is greater than the ULN but less than or equal to 2.5
      x ULN, then the AST must be less than or equal to the ULN. If the AST is greater
      than the ULN but less than or equal to 1.5 x ULN, then the alkaline phosphatase
      must be less than or equal to ULN.

      - Note: If alanine aminotransferase (ALT) is performed instead of AST (per
      institution's standard practice), the ALT value must be less than or equal to 1.5
      x ULN; if both were performed, the AST must be less than or equal to 1.5 x ULN.

   - Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion
   in the study if liver imaging (CT, MRI, PET-CT, or PET scan performed within 90 days
   prior to randomization) does not demonstrate metastatic disease and the requirements
   for adequate hepatic function as described above are met.

   - Patients with alkaline phosphatase that is greater than ULN but less than or equal to
   2.5 x ULN are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET
   scan performed within 90 days prior to randomization does not demonstrate metastatic

   - The most recent postoperative serum creatinine performed within 6 weeks prior to
   randomization must be less than or equal to ULN for the lab.

   - Left ventricular ejection fraction (LVEF) assessment by 2-D echocardiogram or
   multigated acquisition (MUGA) scan must be performed within 90 days prior to
   randomization. The LVEF must be greater than or equal to 50% regardless of the
   facility's lower limit of normal (LLN). (If the facility performing the assessment has
   not reported the LVEF as a whole number, decimals reported as greater than or equal to
   5 should be rounded up and decimals reported as less than 5 should be rounded down.)

Exclusion criteria:

Patients with one or more of the following conditions are ineligible for this study.

   - T4 tumors including inflammatory breast cancer.

   - Definitive clinical or radiologic evidence of metastatic disease. (Chest imaging
   [mandatory for all patients] and other imaging [if required] must have been performed
   within 90 days prior to randomization.)

   - Synchronous or previous contralateral invasive breast cancer. (Patients with
   synchronous and/or previous contralateral DCIS are eligible.)

   - Any history of ipsilateral invasive breast cancer or ipsilateral DCIS.

   - History of non-breast malignancies within 5 years prior to randomization, except for
   the following: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma
   in situ, and basal cell and squamous cell carcinomas of the skin.

   - Previous therapy with anthracyclines or taxanes for any malignancy.

   - Chemotherapy administered for the currently diagnosed breast cancer prior to

   - Continued endocrine therapy such as raloxifene or tamoxifen (or other SERM) or an
   aromatase inhibitor. Patients are eligible if these medications are discontinued prior
   to randomization.

   - Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement
   therapy. Patients are eligible if these medications are discontinued prior to

   - Known active hepatitis B or hepatitis C with abnormal liver function tests.

   - Cardiac disease (history of and/or active disease) that would preclude the use of the
   drugs included in the treatment regimens. This includes but is not confined to:

      - Active cardiac disease

      - angina pectoris that requires the use of anti-anginal medication;

      - ventricular arrhythmias except for benign premature ventricular contractions;

      - supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
      with medication;

      - conduction abnormality requiring a pacemaker;

      - valvular disease with documented compromise in cardiac function;

      - symptomatic pericarditis.

      - History of cardiac disease

      - myocardial infarction documented by elevated cardiac enzymes or persistent
      regional wall abnormalities on assessment of left ventricular function;

      - history of documented congestive heart failure (CHF);

      - documented cardiomyopathy.

   - Whole breast radiation therapy (RT) prior to randomization or partial breast RT that
   cannot be completed on or before the date of randomization.

   - Intrinsic lung disease resulting in dyspnea.

   - Unstable diabetes mellitus.

   - Active infection or chronic infection requiring suppressive antibiotics.

   - History of a major organ allograft or condition requiring chronic immunosuppression,
   e.g., kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases.
   (Patients who have received corneal transplants, cadaver skin, or bone transplants are

   - Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral
   sensory neuropathy) greater than or equal to grade 2, per the NCI CTCAE v4.0.

   - Conditions that would prohibit administration of corticosteroids.

   - Chronic daily treatment with corticosteroids (dose of greater than or equal to 10
   mg/day methylprednisolone equivalent) (excluding inhaled steroids).

   - History of hypersensitivity reaction to drugs formulated with polysorbate 80.

   - Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing must be
   performed within 2 weeks prior to randomization according to institutional standards
   for women of childbearing potential.)

   - Other non-malignant systemic disease that would preclude the patient from receiving
   study treatment or would prevent required follow-up.

   - Psychiatric or addictive disorders or other conditions that, in the opinion of the
   investigator, would preclude the patient from meeting the study requirements.

   - Use of any investigational product within 30 days prior to randomization.


drug: paclitaxel

drug: docetaxel

drug: cyclophosphamide

drug: Doxorubicin

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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