Neoadjuvant Chemotherapy Using Doxorubicin and Paclitaxel in Treating Women With Large Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as doxorubicin and paclitaxel, work in different
      ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy
      before and after surgery may shrink the tumor so it can be removed and may kill any tumor
      cells remaining after surgery.

      PURPOSE: This randomized phase II trial is comparing two different regimens of doxorubicin
      and paclitaxel to see how well they work in treating women who are undergoing surgery for
      breast cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine whether tumors in women with palpable invasive breast cancer with wild type
           p53 are more sensitive to doxorubicin than to paclitaxel when given as sequential
           single-agent neoadjuvant chemotherapy.

        -  Determine whether tumors with inactivated p53 are more sensitive to paclitaxel than to
           doxorubicin when given as sequential single-agent neoadjuvant chemotherapy in these
           patients.

      Secondary

        -  Correlate other biological markers (physiological and molecular) with tumor response in
           patients treated with these regimens.

        -  Determine changes in these biological markers during and after neoadjuvant chemotherapy
           in these patients.

        -  Compare breast MRI, in terms of assessing tumor response, with physical exam, mammogram,
           and ultrasound in patients treated with these regimens.

        -  Determine whether there are MRI indicators (e.g., tumor morphology or lesion
           enhancement) that are predictive of response in patients treated with these regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor
      size (> 5 cm vs ≤ 3-5 cm) and presence of palpable regional lymph nodes (yes vs no). Patients
      are randomized to 1 of 2 treatment arms.

      All patients undergo biopsy, bilateral mammogram, MRI, ultrasound, blood marker, molecular
      (gene microarrays and functional p53 status), and physiologic studies before initiation of
      neoadjuvant chemotherapy. Some of these studies are repeated after completion of treatment
      with the first chemotherapeutic agent and after completion of treatment with the second
      chemotherapeutic agent as outlined below.

        -  Arm I: Patients receive doxorubicin IV on days 1, 15, 29, and 43. Patients with no
           residual tumor (indicated by clinical evaluation and radiologic studies) after
           completion of doxorubicin undergo definitive surgery. After surgery, patients receive
           paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.

      Patients with residual tumor > 2 cm after completion of doxorubicin undergo 8-12 core needle
      biopsies. Patients with residual tumor < 2 cm after completion of doxorubicin undergo 4-6
      core needle biopsies. After core needle biopsies, patients receive paclitaxel as above.

        -  Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50,
           and 57. Patients with no residual tumor (indicated by clinical evaluation and radiologic
           studies) after completion of paclitaxel undergo definitive surgery. After surgery,
           patients receive doxorubicin IV on days 1, 15, 29, and 43.

      Patients with residual tumor > 2 cm after completion of paclitaxel undergo 8-12 core needle
      biopsies. Patients with residual tumor < 2 cm after completion of paclitaxel undergo 4-6 core
      needle biopsies. After core needle biopsies, patients receive doxorubicin as above.

      In both arms, treatment continues in the absence of disease progression or unacceptable
      toxicity.

      Samples from core needle biopsies are analyzed by microarray analysis for gene expression
      profiles.

      Patients are followed every 6 months for 5 years.

      PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this
      study within 4-5 years.
    

Intervention name(s): Doxorubicin followed by Paclitaxel; Paclitaxel followed by Doxorubicin
Intervention type(s): Other; Other
Intervention description(s): Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy:
Doxorubicin followed by Paclitaxel Paclitaxel followed by Doxorubicin; Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy:
Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Doxorubicin; Liposomal doxorubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer