High-Dose Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining peripheral stem cell transplantation with chemotherapy
      may kill more tumor cells.

      PURPOSE: Phase I/II trial to study the effectiveness of high-dose combination chemotherapy
      and peripheral stem cell transplantation in treating patients with recurrent or metastatic
      breast cancer.
    

Detailed description: 
      OBJECTIVES: I. Define the maximum tolerated doses of four courses of doxorubicin (DOX),
      paclitaxel (TAX), and cyclophosphamide (CTX) followed by peripheral blood stem cell (PBSC)
      and granulocyte colony-stimulating factor support given in an out-patient setting in patients
      with metastatic breast cancer. II. Evaluate the cardiotoxicity of the combination of bolus
      DOX, a 3-hour infusion of TAX, and CTX. III. Determine the clinical response rate and time to
      progression associated with this regimen. IV. Determine Cmax, AUC and the drug:metabolite
      ratio of TAX and DOX when given with CTX, a known p450 inducer.

      OUTLINE: Patients without prior doxorubicin (DOX) or paclitaxel (TAX) receive two courses of
      induction chemotherapy with DOX/TAX with G-CSF support given 3 weeks apart. Peripheral blood
      stem cells (PBSC) are harvested during the recovery phase following the second course.
      Patients who previous received DOX or TAX and responded receive cyclophosphamide (CTX) with
      G-CSF for stem cell mobilization followed by PBSC harvest. Back-up bone marrow may be
      harvested from patients without marrow involvement for whom PBSC collection is inadequate.
      Patients with responding or stable disease who have adequate PBSC available receive
      dose-intensive chemotherapy with DOX, CTX, and TAX given on day 1, with PBSC infused on day 3
      and G-CSF given from day 3 until neutrophil recovery. Four courses of dose-intensive
      chemotherapy with PBSC and G-CSF support are given every 3-4 weeks. During the phase I
      portion of the study, groups of 3-6 patients are treated at increasing doses of DOX, TAX, and
      CTX until the maximum tolerated dose (MTD) is determined; during the phase II portion,
      additional patients are treated at the MTD. Patients who progress after 2 courses of
      induction or 2 courses of dose-intensive chemotherapy are given the option of receiving their
      PBSC after conditioning with a different regimen (e.g., CTX, etoposide, and cisplatin).
      Patients who receive induction on protocol but who choose not to receive dose-intensive
      chemotherapy continue DOX/TAX for a total of 6 courses. Patients are followed 3, 6, 12, 18,
      and 24 months after therapy, then as clinically indicated.

      PROJECTED ACCRUAL: During the phase I portion of the study, groups of 3-6 patients will be
      entered at each dose level studied. During the phase II portion of the study, 25 patients
      will be treated at the maximum tolerated dose.
    

Intervention name(s): Filgrastim (G-CSF); Cyclophosphamide; Doxorubicin Hydrochloride; Paclitaxel; Peripheral Blood Stem Cell Transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Procedure
Other intervention name(s): Neupogen; Cytoxan; Neosar; Adriamycin PFS; Adriamycin RDF; Taxol; PBSCT; Stem Cell Transplant; SCT
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV breast cancer; recurrent breast cancer