A Multicenter Phase III Randomized Trial Comparing Docetaxel (Taxotere) and Trastuzumab (Herceptin) With Docetaxel (Taxotere), Carboplatin and Trastuzumab (Herceptin) as First Line Chemotherapy for Patients With Advanced Breast Cancer Containing the HER2 Gene Amplification
- 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
- Compare the response rate and duration of overall response in patients treated with
- 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
- 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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Evaluate time to disease progression after treatment with either Herceptin in with single-agent docetaxel (TH) or Herceptin with Carboplatin and TH in metastatic breast cancer pts previously untreated with chemo whose cancer contains the HER2 gene amp.
till disease progression
Linnea Chap, MD
C. Klien and Associates
United States: Food and Drug Administration
|Jonsson Comprehensive Cancer Center, UCLA||Los Angeles, California 90095-1781|