Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with trastuzumab and lapatinib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving doxorubicin together with cyclophosphamide followed by paclitaxel, trastuzumab, and lapatinib works in treating patients with HER2/neu-overexpressed breast cancer.
Drug: doxorubicin hydrochloride
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Dose-Dense Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/NEU-Overexpressed/Amplified Breast Cancer: Feasibility|
- Feasibility [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Time to recurrence [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||March 2007|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
Experimental: AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB
The regimen consists of AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 4 with pegfilgrastim, followed by weekly paclitaxel (80 mg/m2) x 12 + trastuzumab (H) + lapatinib (L). Pegfilgrastim 6mg is given subcutaneously (SQ) on day # 2 of each AC. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion. Trastuzumab will be administered weekly starting with paclitaxel treatment # 1. Near the completion of all chemotherapy, patients may receive trastuzumab on a q 3-weekly schedule, starting as early as with paclitaxel cycle # 12. The total duration of trastuzumab from beginning to end is 52 weeks. Lapatinib will be given orally at 1000 mg daily, starting with trastuzumab for a total duration of 52 weeks. Hormonal therapy such as tamoxifen or an aromatase inhibitor will be given to patients with hormone receptor positive disease at the physician's discretion. Radiation therapy to the breast or chest is recommended to patients as appropriate.
|Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: lapatinib ditosylate Drug: paclitaxel Other: laboratory biomarker analysis|
- Determine the feasibility of dose-dense doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel, trastuzumab (Herceptin®), and lapatinib ditosylate in patients with HER2/neu-overexpressed/amplified breast cancer.
- Assess the toxicity of this regimen in these patients.
- Determine the time to recurrence in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Explore the use of serial troponin I (cTnI) and C-reactive protein (CRP) as a predictor of cardiac toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study. Patients may receive therapy as neoadjuvant or adjuvant administration. Chemotherapy must be completed before breast surgery in case of neoadjuvant therapy. Adjuvant therapy must begin within 84 days after breast surgery.
- Chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 2 weeks for 4 courses. Patients then receive paclitaxel IV once weekly for 12 weeks.
- Trastuzumab (Herceptin®) and lapatinib ditosylate: Beginning concurrently with paclitaxel, patients receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks and then once every 3 weeks, beginning at least 1 week after completion of paclitaxel, for a total of 52 weeks. Patients also receive oral lapatinib ditosylate once daily, beginning concurrently with paclitaxel, for a total of 52 weeks.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, every 2 weeks during chemotherapy, and at 6, 9, and 18 months. Samples are examined for serial troponin and C-reactive protein.
After completion of study treatment, patients are followed every 3-6 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00482391
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|Principal Investigator:||Chau T. Dang, MD||Memorial Sloan Kettering Cancer Center.|
|Principal Investigator:||Clifford A. Hudis, MD||Memorial Sloan Kettering Cancer Center.|