NCT00004067

Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2

A Randomized Trial Comparing the Safety and Efficacy of Adriamycin and Cyclophosphamide Followed by Taxol (AC-T) to That of Adriamycin and Cyclophosphamide Followed by Taxol Plus Herceptin (AC-T+H) in Node-Positive Breast Cancer Patients Who Have Tumors That Overexpress HER2

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,130 (actual)
• Sponsor: NSABP Foundation Inc · Network
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, 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 whether combination chemotherapy plus trastuzumab is more effective than combination chemotherapy alone for treating breast cancer. PURPOSE: This randomized phase III trial is studying how well giving combination chemotherapy together with trastuzumab works compared to combination chemotherapy alone in treating women with node-positive stage II or stage IIIA breast cancer that overexpresses HER2.

Detailed description

OBJECTIVES: * Compare the cardiotoxicity of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab (Herceptin®) in women with operable, node-positive breast cancer that overexpresses HER2. * Compare the effect of these regimens on disease-free and overall survival of these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (1-3 vs 4-9 vs 10 or more), administration of hormonal therapy (tamoxifen vs anastrozole vs neither), surgery/radiotherapy (lumpectomy plus breast irradiation vs lumpectomy plus breast irradiation plus regional irradiation vs mastectomy without radiotherapy vs mastectomy with radiotherapy), paclitaxel schedule (every 3 weeks vs weekly), and participating center. Patients are randomized to one of two treatment arms. * Arm 1: Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses. Approximately 3 weeks after the last course, patients receive paclitaxel IV over 3 hours every 21 days for 4 courses OR paclitaxel IV over 1 hour once weekly for 12 weeks (12 doses). * Arm 2: Patients receive chemotherapy as in arm I and trastuzumab (Herceptin®) IV over 90 minutes on day 1 of the first course of paclitaxel. Trastuzumab is then administered IV over 30 minutes weekly for 51 weeks, beginning on day 8. All patients with estrogen or progesterone receptor-positive tumors receive hormonal therapy\* for at least 5 years, beginning within 3-12 weeks after the last dose of chemotherapy. Patients who have received prior tamoxifen for prevention may be treated with additional tamoxifen for no more than 5 years at the discretion of the principal investigator (PI). NOTE: \*Other hormonal therapeutic agents are allowed in sequence with or as an alternative to tamoxifen therapy. All patients previously treated with lumpectomy undergo breast irradiation beginning after completion of chemotherapy and concurrently with trastuzumab (in arm 2) administration. Patients previously treated with mastectomy may also receive radiotherapy. Radiotherapy is administered daily for 5-6 weeks. Patients are followed every 6 months for 5 years and then annually thereafter. PROJECTED ACCRUAL: A total of 2,700 patients will be accrued for this study within 4.75 years.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	herceptin	4 mg/kg loading dose then 2 mg/kg weekly for 1 year.
DRUG	adriamycin	60 mg/m2 IV push every 21 days for 4 cycles.
DRUG	cyclophosphamide	600 mg/m2 IV every 21 days for 4 cycles
DRUG	taxol	175 mg/m2 IV every 21 days for 4 cycles

Timeline

• Start date: 2000-02-01
• Primary completion: 2005-03-01
• Completion: 2019-11-01
• First posted: 2003-01-27
• Last updated: 2021-04-29

Locations

149 sites across 2 countries: United States, Canada