Trials / Completed

CompletedNCT01275677

Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer

A Randomized Phase III Trial of Adjuvant Therapy Comparing Chemotherapy Alone (Six Cycles of Docetaxel Plus Cyclophosphamide or Four Cycles of Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel) to Chemotherapy Plus Trastuzumab in Women With Node-Positive or High-Risk Node-Negative HER2-Low Invasive Breast Cancer

Status: Completed
Phase: Phase 3
Study type: Interventional
Enrollment: 3,270 (actual)

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

Summary

This randomized phase III clinical trial studies chemotherapy with or without trastuzumab after surgery to see how well they work in treating women with invasive breast cancer. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving chemotherapy after surgery may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block cancer 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. It is not yet known whether combination chemotherapy is more effective with trastuzumab in treating breast cancer.

Detailed description

PRIMARY OBJECTIVES: I. To determine whether the addition of trastuzumab to chemotherapy (TC or AC→WP) improves invasive disease-free survival (IDFS) in women with resected node-positive or high-risk node-negative breast cancer which is reported as human epidermal growth factor receptor (HER)2-low by all HER2 testing performed. SECONDARY OBJECTIVES: I. To determine whether the addition of trastuzumab to chemotherapy (TC or AC→WP) improves disease-free survival (DFS)-ductal carcinoma in situ (DCIS) in women with resected node-positive or high-risk node-negative breast cancer which is reported as HER2-low by all HER2 testing performed. II. To determine whether the addition of trastuzumab to chemotherapy (TC or AC→WP) improves breast cancer-free survival (BCFS) in women with resected node-positive or high-risk node-negative breast cancer which is reported as HER2-low by all HER2 testing performed. III. To determine whether the addition of trastuzumab to chemotherapy (TC or AC→WP) improves recurrence-free interval (RFI) in women with resected node-positive or high-risk node-negative breast cancer which is reported as HER2-low by all HER2 testing performed. IV. To determine whether the addition of trastuzumab to chemotherapy (TC or AC→WP) improves distant recurrence-free interval (DRFI) in women with resected node-positive or high-risk node-negative breast cancer which is reported as HER2-low by all HER2 testing performed. V. To determine whether the addition of trastuzumab to chemotherapy (TC or AC→WP) improves overall survival (OS) in women with resected node-positive or high-risk node-negative breast cancer which is reported as HER2-low by all HER2 testing performed. VI. To evaluate the associations between amenorrhea and circulating reproductive hormone levels, and the associations between chemotherapy regimen, amenorrhea, and IDFS benefit in premenopausal women eligible at baseline for the menstrual history assessments. VII. To evaluate the toxicity associated with each of the regimens. VIII. To test the hypothesis that the HER2 messenger ribonucleic acid (mRNA) level is the predictor of the degree of benefit from trastuzumab and the threshold for benefit in the adjuvant setting is lower than defined by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines for HER2 assays (immunohistochemistry \[IHC\] and fluorescent in situ hybridization \[FISH\]). IX. To identify and/or validate molecular predictors of the degree of benefit from the addition of trastuzumab to chemotherapy (TC or AC→WP). X. To test the alternative hypothesis that the main determinant of trastuzumab response in the adjuvant setting of HER2-low breast cancer is through antibody-dependent cellular cytotoxicity (ADCC) by demonstrating that the polymorphism of the Fcgamma receptor gene is predictive of the degree of benefit from the addition of trastuzumab to chemotherapy (TC or AC→WP). XI. To examine the relationship between behavioral host factors (obesity, tobacco, alcohol) and comorbid conditions that may influence systemic inflammation and breast cancer outcomes, controlling for tumor/stage characteristics and treatment assignment. XII. To examine the relationship between medication exposures that may influence systemic inflammation and breast cancer outcomes, controlling for tumor/stage characteristics and treatment assignment. XIII. To examine the relationship between comorbid conditions, medication exposures, and behavioral host factors together and breast cancer outcomes, controlling for tumor/stage characteristics and treatment assignment. OUTLINE: Patients are randomized to 1 of 2 treatment arms. NOTE: \*Chemotherapy regimen is based on the investigator's preference. ARM I: GROUP IA: Patients receive docetaxel intravenously (IV) over 60 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. GROUP IB: Patients receive doxorubicin hydrochloride IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2-3 weeks after last dose of doxorubicin hydrochloride and cyclophosphamide, patients also receive paclitaxel IV over 60 minutes once weekly for 12 doses in the absence of disease progression or unacceptable toxicity. ARM II: GROUP IIA: Patients receive docetaxel and cyclophosphamide as in Group IA. Patients also receive trastuzumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. GROUP IIB: Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in Group IB. Patients also receive trastuzumab IV over 30-90 minutes weekly for 12 doses and then every 3 weeks for subsequent doses. Treatment repeats every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 5 years and then every 12 months for 5 years.

Conditions

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Docetaxel	Given IV
DRUG	Doxorubicin	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Paclitaxel	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
BIOLOGICAL	Trastuzumab	Given IV

Timeline

Start date: 2011-02-08
Primary completion: 2017-07-31
Completion: 2025-06-02
First posted: 2011-01-12
Last updated: 2025-07-14
Results posted: 2020-09-23

Locations

1,283 sites across 4 countries: United States, Canada, Ireland, Puerto Rico

Source: ClinicalTrials.gov record NCT01275677. Inclusion in this directory is not an endorsement.