Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00016276
Status:
TERMINATED
Last Update Posted:
2013-01-16
First Post:
2001-05-06
Brief Title:
Combination Chemotherapy Surgery and Radiation Therapy With or Without Dexrazoxane and Trastuzumab in Treating Women With Stage III or Stage IV Breast Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A 2X2X2 Factorial Randomized Phase III Trial Of Multimodality Therapy Comparing 4 Cycles Of Doxorubicin And Cyclophosphamide With Or Without Dexrazoxane AC-Z Followed By 12 Weeks Of Weekly Paclitaxel With Or Without Trastuzumab T-H Followed By Local Therapy Followed By 40 Weeks Of Weekly Trastuzumab Or None In Women With HER-2 STAGE IIIA IIIB OR REGIONAL STAGE IV BREAST CANCER
Status:
TERMINATED
Status Verified Date:
2013-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Administratively complete
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Randomized phase III trial to compare the effectiveness of combination chemotherapy surgery and radiation therapy with or without dexrazoxane and trastuzumab in treating women who have stage IIIA stage IIIB or stage IV breast cancer Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of chemotherapy Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells Radiation therapy uses high-energy x-rays to damage tumor cells It is not yet known if chemotherapy combined with surgery and radiation therapy is more effective with or without dexrazoxane and trastuzumab in treating breast cancer
Detailed Description:
OBJECTIVES
I Determine the time to locoregional recurrence time to completion of treatment and overall survival in women with HER-2 stage IIIA or IIIB or regional stage IV breast cancer treated with doxorubicin and cyclophosphamide with or without dexrazoxane followed by paclitaxel with or without trastuzumab Herceptin followed by surgery and radiotherapy with or without trastuzumab
II Determine whether addition of trastuzumab to paclitaxel therapy improves response at 24 weeks of therapy in these patients
III Determine whether addition of trastuzumab to paclitaxel therapy increases the rate of cardiotoxicity in these patients
IV Determine whether addition of dexrazoxane to doxorubicin and cyclophosphamide compromises response in these patients
V Determine whether addition of dexrazoxane to doxorubicin and cyclophosphamide reduces the rate of cardiotoxicity in these patients
VI Determine whether long-term trastuzumab after local therapy improves disease-free survival in these patients
VII Determine whether long-term trastuzumab after local therapy increases the rate of cardiotoxicity in these patients
VIII Determine the occurrence of any grade 3 or higher toxicity second malignancies acute myelogenous leukemia or myelodysplastic syndrome in patients treated with these regimens
IX Determine the eventual rate of breast conservation in those patients considered candidates for breast conservation prior to neoadjuvant treatment
X Determine the clinical response after doxorubicin and cyclophosphamide with or without dexrazoxane and the clinicalmammographicultrasound response after paclitaxel with or without trastuzumab compared to the pathologic response at definitive surgery in these patients
OUTLINE This is a randomized open-label multicenter study Patients are stratified according to stage inflammatory vs noninflammatory inoperable stage III regional stage IV vs operable stage III Patients are randomized to 1 of 8 treatment arms
Arm I Patients receive dexrazoxane IV over 10-20 minutes doxorubicin IV over 5-10 minutes and cyclophosphamide IV over 30 minutes on days 1 22 43 and 64 Patients receive paclitaxel IV over 1 hour and trastuzumab Herceptin IV over 30-90 minutes on days 85 92 99 106 113 120 127 134 141 148 155 and 162 Approximately 1-2 weeks after completion of neoadjuvant chemotherapy patients undergo breast conservation surgery modified radical mastectomy or mastectomy Patients with unacceptable toxicity or locoregional disease progression may undergo surgery prior to week 24 ie completion of neoadjuvant chemotherapy Beginning 2-4 weeks after breast conservation surgery or 3-5 weeks after mastectomy patients undergo radiotherapy daily 5 days a week for 6-8 weeks Patients receive long-term trastuzumab IV over 30-90 minutes weekly for 40 weeks beginning on week 36 day 254
Arm II Patients receive dexrazoxane doxorubicin and cyclophosphamide as in arm I Patients receive paclitaxel without trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients receive long-term trastuzumab as in arm I
Arm III Patients receive dexrazoxane doxorubicin and cyclophosphamide as in arm I Patients receive paclitaxel and trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients undergo observation only for 40 weeks after completion of radiotherapy
Arm IV Patients receive dexrazoxane doxorubicin and cyclophosphamide as in arm I Patients receive paclitaxel as in arm II Patients undergo surgery and radiotherapy as in arm I Patients undergo observation as in arm III
Arm V Patients receive doxorubicin and cyclophosphamide without dexrazoxane as in arm I Patients receive paclitaxel and trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients receive long-term trastuzumab as in arm I
Arm VI Patients receive doxorubicin and cyclophosphamide as in arm V Patients receive paclitaxel as in arm II Patients undergo surgery and radiotherapy as in arm I Patients receive long-term trastuzumab as in arm I
Arm VII Patients receive doxorubicin and cyclophosphamide as in arm V Patients receive paclitaxel and trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients undergo observation as in arm III
Arm VIII Patients receive doxorubicin and cyclophosphamide as in arm V Patients receive paclitaxel as in arm II Patients undergo surgery and radiotherapy as in arm I Patients undergo observation as in arm III
Treatment continues in all arms in the absence of distant disease progression Beginning within 12 weeks of completion of neoadjuvant chemotherapy hormone receptor-positive patients may receive oral tamoxifen daily for 5 years
Patients are followed every 6 months for 5 years and then annually for 5 years
PROJECTED ACCRUAL A total of 396 patients will be accrued for this study within 4 years
I Determine the time to locoregional recurrence time to completion of treatment and overall survival in women with HER-2 stage IIIA or IIIB or regional stage IV breast cancer treated with doxorubicin and cyclophosphamide with or without dexrazoxane followed by paclitaxel with or without trastuzumab Herceptin followed by surgery and radiotherapy with or without trastuzumab
II Determine whether addition of trastuzumab to paclitaxel therapy improves response at 24 weeks of therapy in these patients
III Determine whether addition of trastuzumab to paclitaxel therapy increases the rate of cardiotoxicity in these patients
IV Determine whether addition of dexrazoxane to doxorubicin and cyclophosphamide compromises response in these patients
V Determine whether addition of dexrazoxane to doxorubicin and cyclophosphamide reduces the rate of cardiotoxicity in these patients
VI Determine whether long-term trastuzumab after local therapy improves disease-free survival in these patients
VII Determine whether long-term trastuzumab after local therapy increases the rate of cardiotoxicity in these patients
VIII Determine the occurrence of any grade 3 or higher toxicity second malignancies acute myelogenous leukemia or myelodysplastic syndrome in patients treated with these regimens
IX Determine the eventual rate of breast conservation in those patients considered candidates for breast conservation prior to neoadjuvant treatment
X Determine the clinical response after doxorubicin and cyclophosphamide with or without dexrazoxane and the clinicalmammographicultrasound response after paclitaxel with or without trastuzumab compared to the pathologic response at definitive surgery in these patients
OUTLINE This is a randomized open-label multicenter study Patients are stratified according to stage inflammatory vs noninflammatory inoperable stage III regional stage IV vs operable stage III Patients are randomized to 1 of 8 treatment arms
Arm I Patients receive dexrazoxane IV over 10-20 minutes doxorubicin IV over 5-10 minutes and cyclophosphamide IV over 30 minutes on days 1 22 43 and 64 Patients receive paclitaxel IV over 1 hour and trastuzumab Herceptin IV over 30-90 minutes on days 85 92 99 106 113 120 127 134 141 148 155 and 162 Approximately 1-2 weeks after completion of neoadjuvant chemotherapy patients undergo breast conservation surgery modified radical mastectomy or mastectomy Patients with unacceptable toxicity or locoregional disease progression may undergo surgery prior to week 24 ie completion of neoadjuvant chemotherapy Beginning 2-4 weeks after breast conservation surgery or 3-5 weeks after mastectomy patients undergo radiotherapy daily 5 days a week for 6-8 weeks Patients receive long-term trastuzumab IV over 30-90 minutes weekly for 40 weeks beginning on week 36 day 254
Arm II Patients receive dexrazoxane doxorubicin and cyclophosphamide as in arm I Patients receive paclitaxel without trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients receive long-term trastuzumab as in arm I
Arm III Patients receive dexrazoxane doxorubicin and cyclophosphamide as in arm I Patients receive paclitaxel and trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients undergo observation only for 40 weeks after completion of radiotherapy
Arm IV Patients receive dexrazoxane doxorubicin and cyclophosphamide as in arm I Patients receive paclitaxel as in arm II Patients undergo surgery and radiotherapy as in arm I Patients undergo observation as in arm III
Arm V Patients receive doxorubicin and cyclophosphamide without dexrazoxane as in arm I Patients receive paclitaxel and trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients receive long-term trastuzumab as in arm I
Arm VI Patients receive doxorubicin and cyclophosphamide as in arm V Patients receive paclitaxel as in arm II Patients undergo surgery and radiotherapy as in arm I Patients receive long-term trastuzumab as in arm I
Arm VII Patients receive doxorubicin and cyclophosphamide as in arm V Patients receive paclitaxel and trastuzumab as in arm I Patients undergo surgery and radiotherapy as in arm I Patients undergo observation as in arm III
Arm VIII Patients receive doxorubicin and cyclophosphamide as in arm V Patients receive paclitaxel as in arm II Patients undergo surgery and radiotherapy as in arm I Patients undergo observation as in arm III
Treatment continues in all arms in the absence of distant disease progression Beginning within 12 weeks of completion of neoadjuvant chemotherapy hormone receptor-positive patients may receive oral tamoxifen daily for 5 years
Patients are followed every 6 months for 5 years and then annually for 5 years
PROJECTED ACCRUAL A total of 396 patients will be accrued for this study within 4 years
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 |
|---|---|---|---|
| CLB-49808 | None | None | None |
| U10CA031946 | NIH | None | None |
| CDR0000068617 | REGISTRY | PDQ Physician Data Query | httpsreporternihgovquickSearchU10CA031946 |