Doxorubicin, Cyclophosphamide, and/or Paclitaxel in Treating Women With Nonmetastatic Breast Cancer

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University Identifier:
First received: August 16, 2005
Last updated: December 8, 2015
Last verified: November 2015

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well doxorubicin, cyclophosphamide, and/or paclitaxel work in treating women with nonmetastatic breast cancer.

Condition Intervention
Breast Cancer
Drug: cyclophosphamide
Drug: doxorubicin
Drug: paclitaxel

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacogenomics Study for Breast Cancer Patients Undergoing Adjuvant Chemotherapy With Doxorubicin (A)/Cyclophosphamide ©) and/or Weekly Paclitaxel

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Treatment-induced myelosuppression (e.g., neutropenia) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of peripheral neuropathy [ Time Frame: 12 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response (relapse in adjuvant setting) for 10 years after completion of study treatment [ Time Frame: Ten years ] [ Designated as safety issue: No ]

Enrollment: 94
Study Start Date: October 2003
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen 1
Patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.
Drug: cyclophosphamide
Given IV
Other Name: Cytoxan
Drug: doxorubicin
Given IV
Other Name: adriamycin
Experimental: Regimen 2
Patients receive doxorubicin and cyclophosphamide as in regimen 1. Patients then receive paclitaxel IV over 1 hour once weekly for 12 weeks.
Drug: cyclophosphamide
Given IV
Other Name: Cytoxan
Drug: doxorubicin
Given IV
Other Name: adriamycin
Drug: paclitaxel
Given IV
Other Name: taxol

Detailed Description:



  • Determine the pharmacogenomics of adjuvant chemotherapy comprising doxorubicin and cyclophosphamide and/or paclitaxel in women with nonmetastatic invasive breast cancer.
  • Determine treatment-induced myelosuppression (e.g., neutropenia) in patients treated with adjuvant doxorubicin and cyclophosphamide who have polymorphisms in drug activation and metabolism genes.
  • Correlate the incidence of peripheral neuropathy with pharmacogenomic analysis in patients treated with paclitaxel.


  • Determine response (i.e., relapse in the adjuvant setting) during a 10-year follow-up period in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients receive treatment on The Cancer and Leukemia Group B study(CALGB) CALGB-40101 OR are assigned to receive 1 of 2 treatment regimens on this study.

  • Regimen 1: Patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.
  • Regimen 2: Patients receive doxorubicin and cyclophosphamide as in regimen 1. Patients then receive paclitaxel IV over 1 hour once weekly for 12 weeks.

After completion of study treatment, patients are followed at 3, 6, and 12 months and then annually for up to 10 years.

PROJECTED ACCRUAL: A total of 500 patients (300 treated with doxorubicin and cyclophosphamide and 200 treated with paclitaxel) will be accrued for this study within 3-4 years.


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

Eligibility Criteria

  • Histologically confirmed invasive breast cancer
  • node negative stage > T1c or T1b with poor prognostic features (high grade, Her2/neu FISH positive, ER negative) or stage 2 (T2, N0) or
  • enrolled on CALGB 40101, CALGB 49909, or the National Cancer Institute of Canada study MA-21 or
  • any node positive patient or locally advanced undergoing neoadjuvant chemotherapy with either AC or paclitaxel
  • Age greater than or equal to 18 years.
  • >/=2 weeks from major surgery (wide excision / lumpectomy / mastectomy)
  • No evidence of systemic metastasis
  • Undergoing adjuvant treatment with standard dose AC or AC followed by weekly Paclitaxel at 80mg/m2
  • Adequate bone marrow, hepatic and renal functions (absolute neutrophil count >1,500/ μl, platelet count > 100,000/ μl, serum creatinine <2.0 mg/dl, total Bilirubin <2.0 x the upper limit of normal (ULN)
  • Ability to answer and understand study surveillance questionnaires
  • No concurrent drug therapy (within 2 weeks) with agents that are known inducers or inhibitors of Cytochrome P450 (CYP450).

Exclusion Criteria

  • Other anticancer cytotoxic or endocrine therapy, immunotherapy, or biologic response modifiers,Study Drugs or other concomitant medications known to cause myelosuppression especially neutropenia and neuropathy
  • Eastern Cooperative Oncology Group Performance Status(ECOG) functional status > 2.
  • Serious co-morbidities including poorly controlled diabetes mellitus, ischaemic heart disease,uncontrolled hypertension or active infection.
  • Pregnancy
  • Use of growth factor during cycle 1 of chemotherapy (AC) under pharmacokinetic evaluation
  • Grade >/=2 peripheral neuropathy symptoms based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) Scale. Exception: a chronic neurologic disorder will be reviewed on a case by case basis by the study PI.
  • Prior treatment with weekly paclitaxelDISEASE CHARACTERISTICS:

    • Histologically confirmed invasive breast cancer, meeting 1 of the following criteria:

      • Node negative disease AND meets 1 of the following stage criteria:

        • Primary tumor > T1c
        • Primary tumor > T1b AND poor prognostic features, defined as the following:

          • High-grade disease
          • Human Epidermal Growth Factor Receptor 2 (HER2)/neu-positive disease by fluorescence in situ hybridization
          • Estrogen receptor-negative disease
        • Stage II disease (T2, N0)
      • Node positive nonmetastatic disease
      • Locally advanced disease AND receiving neoadjuvant chemotherapy comprising doxorubicin and cyclophosphamide OR paclitaxel
      • Enrolled in clinical trial CALGB-40101
    • No evidence of systemic metastasis
    • Hormone receptor status:

      • Not specified
  Contacts and Locations
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Please refer to this study by its identifier: NCT00131963

United States, North Carolina
Duke Cancer Institute
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
National Cancer Institute (NCI)
Principal Investigator: Paul K. Marcom, MD Duke Cancer Institute
  More Information

Responsible Party: Duke University Identifier: NCT00131963     History of Changes
Other Study ID Numbers: Pro00014267  DUMC-4522-04-1-R1  CDR0000438673 
Study First Received: August 16, 2005
Last Updated: December 8, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
stage One A (IA) breast cancer
stage Two (II) breast cancer
stage Three A (IIIA) breast cancer
stage Three B(IIIB) breast cancer
stage Three C(IIIC) breast cancer
stage One B (IB) breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Albumin-Bound Paclitaxel
Liposomal doxorubicin
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Physiological Effects of Drugs
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators processed this record on May 25, 2016