NCT00005970|CompletedPhase 3DMC

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

National Cancer Institute (NCI)ClinicalTrials.gov

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13 other identifiers

NCI-2012-018499343ECOG-N9831CAN-NCIC-MA28SWOG-N9831MA.28NCCTG-N9831CALGB-49909CDR0000067953GUMC-00224N9831U10CA180821U10CA025224

Study Type

interventional

Target

3,436

Locations

4 countries

Sites

157

Timeline

RegisteredJan 2003

StartedMay 2000

CompletionJan 2010

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

3,436

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started May 2000

Longer than P75 for phase_3

Geographic Reach

4 countries

157 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.7 years study duration

Study Start

First participant enrolled

May 19, 2000

Completed

2 months until next milestone

First Submitted

Initial submission to the registry

July 5, 2000

Completed

2.6 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed

2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 25, 2005

Completed

4.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2010

Completed

Last Updated

August 14, 2020

Status Verified

August 1, 2020

Enrollment Period

4.9 years

First QC Date

July 5, 2000

Last Update Submit

August 13, 2020

Conditions

Breast Adenocarcinoma HER2 Positive Breast Carcinoma Stage IA Breast Cancer AJCC v7 Stage IB Breast Cancer AJCC v7 Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage IIIA Breast Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

Duration of DFS
Will be estimated using the Kaplan-Meier method. A stratified log-rank test will be used to assess whether DFS differs with respect to the addition of trastuzumab to a chemotherapy regimen including AC and paclitaxel. Ninety-five percent confidence intervals will be reported for relative risks, for DFS at the 5-year point, and for absolute benefit as defined by differences in DFS and OS.
Time from registration to first adverse event, assessed up to 15 years

Secondary Outcomes (1)

Overall survival
Time from registration to death due to any cause, assessed up to 15 years

Study Arms (3)

Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)

EXPERIMENTAL

Patients receive doxorubicin hydrochloride 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. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or 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.

Drug: Aromatase Inhibition TherapyDrug: CyclophosphamideDrug: Doxorubicin HydrochlorideOther: Laboratory Biomarker AnalysisDrug: PaclitaxelDrug: Tamoxifen Citrate

Arm II (AC, paclitaxel, trastuzumab, tamoxifen)

EXPERIMENTAL

Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab (Herceptin®) 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. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or 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.

Drug: Aromatase Inhibition TherapyDrug: CyclophosphamideDrug: Doxorubicin HydrochlorideOther: Laboratory Biomarker AnalysisDrug: PaclitaxelDrug: Tamoxifen CitrateBiological: Trastuzumab

Arm III (AC, paclitaxel, trastuzumab, tamoxifen)

EXPERIMENTAL

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 ER- or 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.

Drug: Aromatase Inhibition TherapyDrug: CyclophosphamideDrug: Doxorubicin HydrochlorideOther: Laboratory Biomarker AnalysisDrug: PaclitaxelDrug: Tamoxifen CitrateBiological: Trastuzumab