A Pharmacogenomics Study for Breast Cancer Patients Undergoing Adjuvant Chemotherapy With Doxorubicin (A)/Cyclophosphamide ©) and/or Weekly Paclitaxel

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00131963
First received: August 16, 2005
Last updated: July 22, 2016
Last verified: November 2015

August 16, 2005
July 22, 2016
October 2003
October 2014   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00131963 on ClinicalTrials.gov Archive Site
Response (relapse in adjuvant setting) for 10 years after completion of study treatment [ Time Frame: Ten years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
A Pharmacogenomics Study for Breast Cancer Patients Undergoing Adjuvant Chemotherapy With Doxorubicin (A)/Cyclophosphamide ©) and/or Weekly Paclitaxel
A Pharmacogenomics Study for Breast Cancer Patients Undergoing Adjuvant Chemotherapy With Doxorubicin (A)/Cyclophosphamide ©) and/or Weekly Paclitaxel

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.

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:
DNA will be extracted from blood samples taken at the first cycle of Doxorubicin and/or Paclitaxel to analyze certain genes that may predict the severity of side-effects that may be experienced with chemotherapy.
Probability Sample
Subjects will be recruited from the breast cancer oncology clinics.
Breast Cancer
  • Drug: cyclophosphamide
    Given IV
    Other Name: Cytoxan
  • Drug: doxorubicin
    Given IV
    Other Name: adriamycin
  • Drug: paclitaxel
    Given IV
    Other Name: taxol
  • 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin
  • Regimen 2
    Patients receive doxorubicin and cyclophosphamide as in regimen 1. Patients then receive paclitaxel IV over 1 hour once weekly for 12 weeks.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin
    • Drug: paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
94
October 2014
October 2014   (final data collection date for primary outcome measure)

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
Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00131963
Pro00014267, DUMC-4522-04-1-R1, CDR0000438673
No
Not Provided
Not Provided
Duke University
Duke University
National Cancer Institute (NCI)
Principal Investigator: Paul K. Marcom, MD Duke Cancer Institute
Duke University
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP