|First Submitted Date ICMJE||March 12, 2009|
|First Posted Date ICMJE||March 13, 2009|
|Results First Submitted Date||January 12, 2015|
|Results First Posted Date||March 23, 2015|
|Last Update Posted Date||October 19, 2015|
|Start Date ICMJE||May 2009|
|Primary Completion Date||August 2014 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||Pathologic complete response|
|Change History||Complete list of historical versions of study NCT00861705 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Paclitaxel With or Without Carboplatin and/or Bevacizumab Followed by Doxorubicin and Cyclophosphamide in Treating Patients With Breast Cancer That Can Be Removed by Surgery|
|Official Title ICMJE||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-Poor/HER2-Negative Resectable Breast Cancer|
|Brief Summary||This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or 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.|
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)-poor/human 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-poor/HER2(-), 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.
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-poor/HER2(-), 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-poor/HER2(-), 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 and/or 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 and/or 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.
I. To assess whether the impact of the addition of carboplatin and/or bevacizumab to NAC with weekly paclitaxel followed by ddAC on achievement of pathologic CRs in patients with HR-poor/HER2(-), 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, and/or 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 and/or 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 (i.e., 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 Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Publications *||Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||August 2014|
|Primary Completion Date||August 2014 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00861705|
|Other Study ID Numbers ICMJE||NCI-2009-01172
NCI-2009-01172 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CALGB 40603/CTSU 40603
CALGB 40603 ( Other Identifier: Alliance for Clinical Trials in Oncology )
CALGB-40603 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA031946 ( U.S. NIH Grant/Contract )
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Cancer Institute (NCI)|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Cancer Institute (NCI)|
|Verification Date||August 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP