Docetaxel and Trastuzumab With or Without Carboplatin in Treating Women With HER2-Positive Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00047255
- Lead Sponsor
- Jonsson Comprehensive Cancer Center
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 263
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Docetaxel, Carboplatin, and Herceptin trastuzumab 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. Herceptin plus docetaxel trastuxumab 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. Herceptin plus docetaxel Docetaxel 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. Docetaxel, Carboplatin, and Herceptin carboplatin 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. Docetaxel, Carboplatin, and Herceptin Docetaxel 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.
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method To evaluate and compare the rate of clinical benefit, defined as CR, PR, or stable disease > 24 weeks. undefined To evaluate pathologic and molecular markers for predicting efficacy. 2 years Correlate peripheral levels of shed HER2 extracellular domain (ECD) with FISH results and to determine whether peripheral levels of shed HER2 ECD consitute a prognostic and/or predicitive factor vis-a-vis time to progression and survival. undefined To evaluate genetic and biochemical markers for predicting risk of developing cardiac dysfunction and later cardiac events in this patient population. 2 years To compare response rate, duration of overall response, overall survival. undefined To compare toxicity between the 2 arms. 2 years
Trial Locations
- Locations (1)
Jonsson Comprehensive Cancer Center, UCLA
🇺🇸Los Angeles, California, United States