Trial Exploring Feasibility of Densification and Optimal Sequencing of Postoperative Adjuvant Fluorouracil, Epirubicin Plus Cyclophosphamide (FEC) and Docetaxel Chemotherapy in Patients With High Risk Primary Operable Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The rationale of this randomized phase II study is to investigate the feasibility of
      sequenced densified FEC and docetaxel based regimens in patients with primary operable
      high-risk breast cancer. Several phase III and phase II clinical trials showed the benefits
      of dose-dense therapy (Q2W) over conventional treatment in breast cancer, lymphoma and SCLC.
      The aim of the study is also to demonstrate that further shortening of treatment interval
      from 14 days to 10-11 days in FEC regimen is feasible and will not compromise patient's
      safety. The results of this randomized phase II study should serve as a basis for follow-up
      randomized phase III trial comparing conventional versus densified sequential FEC and
      docetaxel based regimens.
    

Detailed description: 
      Arm A:

      The three cycles of conventional FEC followed by three cycles of docetaxel regimen will be
      given at the following doses:

      Fluorouracil 500 mg/m² by i.v. bolus or infusion, Epirubicin 100 mg/m² by 30 minutes i.v.
      infusion and Cyclophosphamide 500 mg/m² by i.v. bolus or infusion followed by docetaxel 100
      mg/m2 i.v. infusion. All drugs will be administered intravenously on Day 1 of each 21-day
      cycle without support of growth factors.

      Pegfilgrastim is only allowed in secondary prophylaxis: febrile neutropenia or prolonged
      grade IV neutropenia. In the event of febrile neutropenia or prolonged grade IV neutropenia,
      pegfilgrastim or filgrastim is given for treatment, and pegfilgrastim should be further
      administered on day 2 of each subsequent cycle of chemotherapy.

      The total duration of treatment is 18 weeks.

      Arm B:

      The three cycles of conventional docetaxel followed by three cycles of FEC regimen will be
      given at the following doses:

      Docetaxel 100 mg/m2 i.v. infusion followed by Fluorouracil 500 mg/m² by i.v. bolus or
      infusion, Epirubicin 100 mg/m² by 30 minutes i.v. infusion and Cyclophosphamide 500 mg/m² by
      i.v. bolus or infusion. All drugs will be administered intravenously on Day 1 of each 21-day
      cycle without support of growth factors.

      Pegfilgrastim is only allowed in secondary prophylaxis: febrile neutropenia or prolonged
      grade IV neutropenia. In the event of febrile neutropenia or prolonged grade IV neutropenia,
      pegfilgrastim or filgrastim is given for treatment, and pegfilgrastim should be further
      administered on day 2 of each subsequent cycle of chemotherapy.

      The total duration of treatment is 18 weeks.

      Arm C:

      The four cycles of dose-dense FEC followed by four cycles dose-dense docetaxel regimen will
      be given at the following doses:

      Fluorouracil 375 mg/m² by i.v. bolus or infusion, Epirubicin 75 mg/m² by 30 minutes i.v.
      infusion and Cyclophosphamide 375 mg/m² by i.v. bolus or infusion followed by docetaxel 75
      mg/m2. FEC regimen will be administered intravenously on Day 1 of each 10-11-day cycle and
      docetaxel will be given on Day 1 of each 14-day cycle.

      Pegfilgrastim (Neulasta) fixed dose of 6 mg (0.6 mL of a 10 mg/mL solution) as a single
      subcutaneous injection will be given in on Day 2 of each study cycle.

      The total duration of treatment is 14 weeks.

      Arm D:

      The four cycles of dose-dense docetaxel followed by four cycles dose-dense FEC regimen will
      be given at the following doses:

      Docetaxel 75 mg/m² followed Fluorouracil 375 mg/m² by i.v. bolus or infusion, Epirubicin 75
      mg/m² by 30 minutes i.v. infusion and Cyclophosphamide 375 mg/m² by i.v. bolus or infusion.
      Docetaxel will be given on Day 1 of each 14-day cycle and FEC regimen will be administered
      intravenously on Day 1 of each 10-11-day cycle.

      Pegfilgrastim (Neulasta) fixed dose of 6 mg (0.6 mL of a 10 mg/mL solution) as a single
      subcutaneous injection will be given on Day 2 of each study cycle.

      The total duration of treatment is 14 weeks.
    

Intervention name(s): dose dense with neulasta
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: breast cancer; adjuvant; dose dense; docetaxel; pegfilgrastim