Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005970
Status:
COMPLETED
Last Update Posted:
2020-08-14
First Post:
2000-07-05
Brief Title:
Doxorubicin Hydrochloride Cyclophosphamide and Pacltaxel With or Without Trastuzumab in Treating Women With HER2-Positive Node-Positive or High-Risk Node-Negative Breast Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
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
Status Verified Date:
2020-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 45 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
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 45 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2012-01849 | REGISTRY | None | None |
| 9343 | None | None | None |
| ECOG-N9831 | None | None | None |
| CAN-NCIC-MA28 | None | None | None |
| SWOG-N9831 | None | None | None |
| MA28 | None | None | None |
| NCCTG-N9831 | None | None | None |
| CALGB-49909 | None | None | None |
| CDR0000067953 | None | None | None |
| GUMC-00224 | None | None | None |
| N9831 | OTHER | None | None |
| N9831 | OTHER | None | None |
| U10CA180821 | NIH | None | None |
| U10CA025224 | NIH | CTEP | httpsreporternihgovquickSearchU10CA025224 |