Trials / Completed

CompletedNCT00005970

Doxorubicin Hydrochloride, Cyclophosphamide, and Pacltaxel With or Without Trastuzumab in Treating Women With HER2-Positive Node-Positive or High-Risk Node-Negative Breast Cancer

Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women With HER-2 Over-Expressing or Amplified Node Positive or High-Risk Node Negative Breast Cancer

Status: Completed
Phase: Phase 3
Study type: Interventional
Enrollment: 3,436 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: Female
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and trastuzumab to see how well they work compared to combination chemotherapy alone in treating women with breast cancer that is human epidermal growth factor receptor 2 (HER2)-positive and has spread to the lymph nodes or high-risk and has not spread to the lymph nodes. 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 whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer.

Detailed description

PRIMARY OBJECTIVES: I. To compare the combination of doxorubicin hydrochloride and cyclophosphamide (AC) followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of disease free survival (DFS). (Stage I) II. To compare the combination of AC followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of the rate of cardiac events. (Stage I) III. To compare the combination AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of DFS. (Stage II) IV. To compare the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of DFS. (Stage II) V. To compare the combination AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of the rate of cardiac events. (Stage II) SECONDARY OBJECTIVES: I. To compare the combination of AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of overall survival (OS). II. To compare the combination AC followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of OS. III. To compare the sequential schedule of the combination AC, weekly paclitaxel, and trastuzumab with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of OS. TERTIARY OBJECTIVES: I. To determine whether higher levels of shed ECD (extracellular domain) or autoantibodies to human epidermal growth factor receptor (HER)-2 and HER-1 measured in the serum prior to treatment are prognostic for DFS and survival. II. To determine the concordance of central review of HER-2 overexpression as measured by the HercepTest (DAKO) and Vysis fluorescence in situ hybridization (FISH). III. For each treatment arm, levels of brain natriuretic peptide (BNP), troponin-T (TnT), troponin-I (cTnI), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 (IL-6), CD40 ligand, and troponin levels will be compared and contrasted. IV. To determine whether genetic markers are prognostic for cardiac adverse events associated with treatment. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM I\*: Patients receive doxorubicin hydrochloride intravenously (IV) and cyclophosphamide IV over 20-30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour beginning on day 1 of week 13 and continuing weekly for 12 courses in the absence of disease progression or unacceptable toxicity. NOTE: \*Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment. ARM II\*: Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab IV over 30-90 minutes beginning on day 1 of week 25 and continuing weekly for 52 courses in the absence of disease progression or unacceptable toxicity. NOTE: \*Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment. ARM III: Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I. Patients then receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes beginning on day 1 of week 13 and continuing weekly for 12 courses. Patients then receive trastuzumab IV over 30 minutes beginning on day 1 of week 25 and continuing weekly for 40 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal estrogen receptor (ER)- or progesterone receptor (PR)-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 15 years or until disease progression.

Conditions

Interventions

Type	Name	Description
DRUG	Aromatase Inhibition Therapy	Given orally
DRUG	Cyclophosphamide	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Paclitaxel	Given IV
DRUG	Tamoxifen Citrate	Given orally
BIOLOGICAL	Trastuzumab	Given IV

Timeline

Start date: 2000-05-19
Primary completion: 2005-04-25
Completion: 2010-01-27
First posted: 2003-01-27
Last updated: 2020-08-14

Locations

157 sites across 4 countries: United States, Canada, Peru, South Africa

Source: ClinicalTrials.gov record NCT00005970. Inclusion in this directory is not an endorsement.