Ignite Creation Date:
2024-05-05 @ 9:22 PM
Last Modification Date:
2024-10-26 @ 10:02 AM
Study NCT ID:
NCT00861705
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-17
First Post:
2009-03-12
Brief Title:
Paclitaxel With or Without Carboplatin andor Bevacizumab Followed by Doxorubicin and Cyclophosphamide in Treating Patients With Breast Cancer That Can Be Removed by Surgery
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin - Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-PoorHER2-Negative Resectable Breast Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
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 II trial studies how well paclitaxel with or without carboplatin andor bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery Drugs used in chemotherapy such as paclitaxel carboplatin doxorubicin and cyclophosphamide work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed
Detailed Description:
PRIMARY OBJECTIVES
I To determine whether adding bevacizumab to neoadjuvant weekly paclitaxel - carboplatin and subsequent dose-dense doxorubicin and cyclophosphamide ddAC significantly raises the rate of pathologic complete response pCR in the breast in patients with hormone receptor HR-poorhuman epidermal growth factor receptor 2 HER2 - resectable breast cancer
II To determine whether adding carboplatin every 3 weeks to neoadjuvant weekly paclitaxel followed by ddAC - bevacizumab significantly raises the rate of pCR in the breast in patients with HR-poorHER2- resectable breast cancer
III To determine whether adding bevacizumab every 2 weeks to neoadjuvant weekly paclitaxel - carboplatin and subsequent ddAC significantly raises the rate of pCR in the breast in patients with basal-like breast cancers as defined by gene expression array
IV To determine whether adding carboplatin every 3 weeks to neoadjuvant weekly paclitaxel followed by ddAC - bevacizumab significantly raises the rate of pCR in the breast in patients with basal-like breast cancers as defined by gene expression array
SECONDARY OBJECTIVES
I To determine the pCR rates in the breast and axilla using American Joint Committee On Cancer AJCC TNM criteria version 6 to neoadjuvant weekly paclitaxel with or without carboplatin followed by ddAC with or without bevacizumab given concurrently with the weekly paclitaxel and ddAC in a patients with HR-poorHER2- resectable breast cancer and b the subset of patients with basal-like breast cancers as defined by gene expression array
II To assess whether there is an interaction between the addition of carboplatin and bevacizumab to neoadjuvant chemotherapy NAC with weekly paclitaxel followed by ddAC as regards the path pCR rates in a patients with HR-poorHER2- resectable breast cancer and b the subset of patients with basal-like breast cancers as defined by gene expression array
III To assess the toxicity of the control regimen weekly paclitaxel followed by ddAC and any incremental toxicities associated with the addition of carboplatin andor bevacizumab in this patient population including the incidence of febrile neutropenia grade 3 thrombocytopenia grade 2 neurotoxicity grade 3 hypertension and clinically significant bleeding or thrombotic including cardiovascular and cerebrovascular events
IV To determine the recurrence-free survival RFS measured from definitive surgery to first event and time to first failure TFF measured from study entry to first event
V To determine overall survival OS defined as time from registration to death from any cause
VI To assess the impact of NAC with weekly paclitaxel followed by ddAC with or without carboplatin andor bevacizumab on axillary lymph node involvement at surgery particularly in patients with clinically or histologically positive axillary lymph nodes prior to initiation of NAC
VII To assess the impact of the addition of bevacizumab to NAC on the incidence and severity of post-op complications especially excessive bleeding delayed wound healing and thrombotic complications
VIII To evaluate residual cancer burden RCB as a predictor of RFS TFF and OS
IX To determine the correlation between clinical radiographic and pathologic response
TERTIARY OBJECTIVES
I To assess whether the impact of the addition of carboplatin andor bevacizumab to NAC with weekly paclitaxel followed by ddAC on achievement of pathologic CRs in patients with HR-poorHER2- resectable breast cancer is influenced by molecular subtype as defined by gene expression array
II To obtain blood fresh frozen and fixed tumor tissue to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in tissue blood and serum that may influence response to and toxicity of weekly paclitaxel ddAC carboplatin andor bevacizumab
III To obtain blood samples to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in blood that may influence response to and toxicity of weekly paclitaxel ddAC carboplatin andor bevacizumab
IV To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy
V To examine the practice patterns and use of sentinel lymphadenectomy pre-chemotherapy or post-chemotherapy in patients with T2 or T3 breast cancer
VI To examine the proportion of patients who presented with T2 or T3 cancers who undergo mastectomy despite cytoreduction adequate for breast conservation
VII To determine the radiotherapy practice patterns for post-mastectomy and regional nodal irradiation in patients undergoing neoadjuvant chemotherapy
OUTLINE Patients are randomized to 1 of 4 treatment arms
ARM I Patients receive paclitaxel intravenously IV over 60 minutes once weekly in weeks 1-12 Patients then receive dose-dense doxorubicin hydrochloride IV over 3-10 minutes and cyclophosphamide IV over 5-60 minutes ddAC once in weeks 13 15 17 and 19
ARM II Patients receive paclitaxel and ddAC as in Arm I Patients also receive bevacizumab IV over 30-90 minutes once in weeks 1 3 5 7 9 11 13 15 and 17
ARM III Patients receive paclitaxel and ddAC as in Arm I Patients also receive carboplatin IV over 30 minutes once in weeks 1 4 7 and 10
ARM IV Patients receive paclitaxel and ddAC as in Arm I bevacizumab as in Arm II and carboplatin as in Arm III
Patients in all arms undergo definitive surgery ie modified radical mastectomy or breast-conserving surgery with appropriate management of the axilla between 4-8 weeks after completion of neoadjuvant therapy
After completion of study treatment patients are followed up periodically for up to 10 years
I To determine whether adding bevacizumab to neoadjuvant weekly paclitaxel - carboplatin and subsequent dose-dense doxorubicin and cyclophosphamide ddAC significantly raises the rate of pathologic complete response pCR in the breast in patients with hormone receptor HR-poorhuman epidermal growth factor receptor 2 HER2 - resectable breast cancer
II To determine whether adding carboplatin every 3 weeks to neoadjuvant weekly paclitaxel followed by ddAC - bevacizumab significantly raises the rate of pCR in the breast in patients with HR-poorHER2- resectable breast cancer
III To determine whether adding bevacizumab every 2 weeks to neoadjuvant weekly paclitaxel - carboplatin and subsequent ddAC significantly raises the rate of pCR in the breast in patients with basal-like breast cancers as defined by gene expression array
IV To determine whether adding carboplatin every 3 weeks to neoadjuvant weekly paclitaxel followed by ddAC - bevacizumab significantly raises the rate of pCR in the breast in patients with basal-like breast cancers as defined by gene expression array
SECONDARY OBJECTIVES
I To determine the pCR rates in the breast and axilla using American Joint Committee On Cancer AJCC TNM criteria version 6 to neoadjuvant weekly paclitaxel with or without carboplatin followed by ddAC with or without bevacizumab given concurrently with the weekly paclitaxel and ddAC in a patients with HR-poorHER2- resectable breast cancer and b the subset of patients with basal-like breast cancers as defined by gene expression array
II To assess whether there is an interaction between the addition of carboplatin and bevacizumab to neoadjuvant chemotherapy NAC with weekly paclitaxel followed by ddAC as regards the path pCR rates in a patients with HR-poorHER2- resectable breast cancer and b the subset of patients with basal-like breast cancers as defined by gene expression array
III To assess the toxicity of the control regimen weekly paclitaxel followed by ddAC and any incremental toxicities associated with the addition of carboplatin andor bevacizumab in this patient population including the incidence of febrile neutropenia grade 3 thrombocytopenia grade 2 neurotoxicity grade 3 hypertension and clinically significant bleeding or thrombotic including cardiovascular and cerebrovascular events
IV To determine the recurrence-free survival RFS measured from definitive surgery to first event and time to first failure TFF measured from study entry to first event
V To determine overall survival OS defined as time from registration to death from any cause
VI To assess the impact of NAC with weekly paclitaxel followed by ddAC with or without carboplatin andor bevacizumab on axillary lymph node involvement at surgery particularly in patients with clinically or histologically positive axillary lymph nodes prior to initiation of NAC
VII To assess the impact of the addition of bevacizumab to NAC on the incidence and severity of post-op complications especially excessive bleeding delayed wound healing and thrombotic complications
VIII To evaluate residual cancer burden RCB as a predictor of RFS TFF and OS
IX To determine the correlation between clinical radiographic and pathologic response
TERTIARY OBJECTIVES
I To assess whether the impact of the addition of carboplatin andor bevacizumab to NAC with weekly paclitaxel followed by ddAC on achievement of pathologic CRs in patients with HR-poorHER2- resectable breast cancer is influenced by molecular subtype as defined by gene expression array
II To obtain blood fresh frozen and fixed tumor tissue to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in tissue blood and serum that may influence response to and toxicity of weekly paclitaxel ddAC carboplatin andor bevacizumab
III To obtain blood samples to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in blood that may influence response to and toxicity of weekly paclitaxel ddAC carboplatin andor bevacizumab
IV To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy
V To examine the practice patterns and use of sentinel lymphadenectomy pre-chemotherapy or post-chemotherapy in patients with T2 or T3 breast cancer
VI To examine the proportion of patients who presented with T2 or T3 cancers who undergo mastectomy despite cytoreduction adequate for breast conservation
VII To determine the radiotherapy practice patterns for post-mastectomy and regional nodal irradiation in patients undergoing neoadjuvant chemotherapy
OUTLINE Patients are randomized to 1 of 4 treatment arms
ARM I Patients receive paclitaxel intravenously IV over 60 minutes once weekly in weeks 1-12 Patients then receive dose-dense doxorubicin hydrochloride IV over 3-10 minutes and cyclophosphamide IV over 5-60 minutes ddAC once in weeks 13 15 17 and 19
ARM II Patients receive paclitaxel and ddAC as in Arm I Patients also receive bevacizumab IV over 30-90 minutes once in weeks 1 3 5 7 9 11 13 15 and 17
ARM III Patients receive paclitaxel and ddAC as in Arm I Patients also receive carboplatin IV over 30 minutes once in weeks 1 4 7 and 10
ARM IV Patients receive paclitaxel and ddAC as in Arm I bevacizumab as in Arm II and carboplatin as in Arm III
Patients in all arms undergo definitive surgery ie modified radical mastectomy or breast-conserving surgery with appropriate management of the axilla between 4-8 weeks after completion of neoadjuvant therapy
After completion of study treatment patients are followed up periodically for up to 10 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 |
|---|---|---|---|
| U10CA031946 | NIH | CTEP | httpsreporternihgovquickSearchU10CA031946 |
| NCI-2009-01172 | REGISTRY | None | None |
| CALGB 40603CTSU 40603 | None | None | None |
| CALGB-40603 | None | None | None |
| CDR0000636850 | None | None | None |
| CALGB 40603 | OTHER | None | None |
| CALGB-40603 | OTHER | None | None |
| U10CA180821 | NIH | None | None |