Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer

Breast Cancer Clinical Trial

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

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT00482391
• Study type: Interventional
• Source: Memorial Sloan Kettering Cancer Center
• Status: Completed
• Phase: Phase 2
• Start date: March 2007
• Completion date: July 2011