Docetaxel and Trastuzumab With or Without Carboplatin in Treating Women With HER2-Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells
      and either kill them or deliver tumor-killing substances to them without harming normal
      cells. It is not yet known if docetaxel and trastuzumab are more effective with or without
      carboplatin in treating women who have HER2-positive breast cancer.

      PURPOSE: Randomized phase III trial to study the effectiveness of combining docetaxel and
      trastuzumab with or without carboplatin in treating women who have HER2-positive stage IIIB
      or stage IV breast cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the time to disease progression in women with HER2-positive stage IIIB, IIIC, or
           IV breast cancer treated with docetaxel and trastuzumab (Herceptin) with or without
           carboplatin.

        -  Compare the response rate and duration of overall response in patients treated with
           these regimens.

        -  Compare the overall survival of patients treated with these regimens.

        -  Compare rate of clinical benefit, defined as complete response, partial response, or
           stable disease for more than 24 weeks, in patients treated with these regimens.

        -  Compare the toxicity of these regimens in these patients.

        -  Determine pathologic and molecular markers for predicting efficacy of these regimens in
           these patients.

        -  Determine genetic and biochemical markers for predicting risk of cardiac dysfunction and
           later cardiac events in patients receiving these regimens.

        -  Determine whether peripheral levels of shed HER2 extracellular domain constitute a
           prognostic and/or predictive factor of time to progression and survival of patients
           receiving these regimens.

      OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
      according to prior adjuvant and/or neoadjuvant chemotherapy (none vs with taxanes vs without
      taxanes) and participating center. Patients are randomized to 1 of 2 treatment arms.

        -  Arm I:

             -  Course 1: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1,
                8, and 15. Patients receive docetaxel IV over 1 hour and carboplatin IV over 30-60
                minutes on day 2.

             -  Courses 2 and all subsequent courses: Patients receive docetaxel IV over 1 hour and
                carboplatin IV over 30-60 minutes on day 1 and trastuzumab IV over 30 minutes on
                days 1, 8, and 15.

        -  Arm II: Patients receive docetaxel and trastuzumab as in arm I. In both arms, treatment
           repeats every 21 days for up to 8 courses in the absence of disease progression or
           unacceptable toxicity. After completion of 8 courses, patients continue to receive
           trastuzumab IV over 30 minutes every 21 days in the absence of disease progression.

      Patients are followed every 2 months for 3 years.

      PROJECTED ACCRUAL: A total of 250 patients (125 per treatment arm) will be accrued for this
      study within 18 months.
    

Intervention name(s): trastuzumab; carboplatin; docetaxel; trastuxumab; Docetaxel
Intervention type(s): Biological; Drug; Drug; Biological; Drug
Intervention description(s): Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose admin by IV over 90 mins, Day 2: Docetaxel (T) 75 mg/m2 by IV over 1 hour followed by carboplatin (C) at target AUC=6 mg/mL/min admin by IV over 30-60 mins, Day 8: (H) 2mg/kg admin by IV over 30 mins, Day 15: 2mg/kg admin by IV over 30 mins.
Subsequent cycles: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins.
Last cycle: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins, Day 22: (H) 6 mg/kg admin by IV over 30 mins.; Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose admin by IV over 90 mins, Day 2: Docetaxel (T) 75 mg/m2 by IV over 1 hour followed by carboplatin (C) at target AUC=6 mg/mL/min admin by IV over 30-60 mins, Day 8: (H) 2mg/kg admin by IV over 30 mins, Day 15: 2mg/kg admin by IV over 30 mins.
Subsequent cycles: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins.
Last cycle: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins, Day 22: (H) 6 mg/kg admin by IV over 30 mins.; Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose administered by IV infusion over 90 minutes, Day 2: Docetaxel (T) 100 mg/m2 by IV infusion over 30 minutes, Day 8: (H) 2mg/kg administered by IV infusion over 30 minutes, Day 15: 2mg/kg administered by IV infusion over 30 minutes.
Subsequent cycles: Day 1: (T) 100mg/m2 as 1 hour IV infusion given every 3 weeks, followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes.
Last cycle: Day 1: (T) 100mg/m2 as 1 hour IV infusion followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 22: (H) 6 mg/kg administered by IV infusion over 30 minutes.; Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose administered by IV infusion over 90 minutes, Day 2: Docetaxel (T) 100 mg/m2 by IV infusion over 30 minutes, Day 8: (H) 2mg/kg administered by IV infusion over 30 minutes, Day 15: 2mg/kg administered by IV infusion over 30 minutes.
Subsequent cycles: Day 1: (T) 100mg/m2 as 1 hour IV infusion given every 3 weeks, followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes.
Last cycle: Day 1: (T) 100mg/m2 as 1 hour IV infusion followed by (H) 2 mg/kg IV infusion over 30 minutes, Day 8: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 15: (H) 2 mg/kg administered by IV infusion over 30 minutes, Day 22: (H) 6 mg/kg administered by IV infusion over 30 minutes.; Cycle 1: Day 1: Herceptin (H) 4 mg/kg loading dose admin by IV over 90 mins, Day 2: Docetaxel (T) 75 mg/m2 by IV over 1 hour followed by carboplatin (C) at target AUC=6 mg/mL/min admin by IV over 30-60 mins, Day 8: (H) 2mg/kg admin by IV over 30 mins, Day 15: 2mg/kg admin by IV over 30 mins.
Subsequent cycles: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins.
Last cycle: Day 1: (T) 75mg/m2 as 1 hour IV followed by (C) at target AUC=6 mg/mL/min admin by IV 30-60 mins every 3 weeks followed by (H) 2 mg/kg IV over 30 mins, Day 8: (H) 2 mg/kg admin by IV over 30 mins, Day 15: (H) 2 mg/kg admin by IV over 30 mins, Day 22: (H) 6 mg/kg admin by IV over 30 mins.
Other intervention name(s): herceptin; taxotere; herceptin; taxotere
Intervention MeSH terms: Carboplatin; Docetaxel; Trastuzumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; recurrent breast cancer