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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00861705
First received: March 12, 2009
Last updated: September 28, 2015
Last verified: August 2015
Results First Received: January 12, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Estrogen Receptor Negative
HER2/Neu Negative
Male Breast Carcinoma
Progesterone Receptor Negative
Stage IIA Breast Cancer
Stage IIB Breast Cancer
Stage IIIA Breast Cancer
Triple-Negative Breast Carcinoma
Interventions: Biological: Bevacizumab
Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm 1 (Pac --> ddAC)

Patients receive paclitaxel (pac) IV over 60 minutes once weekly in weeks 1-12. Patients then receive dose-dense doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 5-30 minutes (ddAC) once in weeks 13, 15, 17, and 19.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

Arm 2 (Pac + Bev --> ddAC + Bev)

Patients receive pac and ddAC as in arm 1. Patients also receive bevacizumab (bev) IV over 30-90 minutes in weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

bevacizumab: Given IV

Arm 3 (Pac + Carboplatin --> ddAC)

Patients receive pac and ddAC as in arm 1. Patients also receive carboplatin IV over 30 minutes once in weeks 1, 4, 7, and 10.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

carboplatin: Given IV

Arm 4 (Pac + Carboplatin + Bev --> ddAC + Bev)

Patients receive pac and ddAC as in arm 1, bev as in arm 2, and carboplatin as in arm 3.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

bevacizumab: Given IV

carboplatin: Given IV


Participant Flow:   Overall Study
    Arm 1 (Pac --> ddAC)     Arm 2 (Pac + Bev --> ddAC + Bev)     Arm 3 (Pac + Carboplatin --> ddAC)     Arm 4 (Pac + Carboplatin + Bev --> ddAC + Bev)  
STARTED     115     113     113     113  
COMPLETED     108     110     113     112  
NOT COMPLETED     7     3     0     1  
Never Began Treatment                 7                 3                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Using a modified intent-to-treat approach only patients who began protocol treatment (n=443) were included in analyses for neoadjuvant treatment and toxicity. Analyses for surgical endpoints excluded 10 patients who withdrew consent prior to surgery (n=433). All analyses considered patients according to treatment assignment.

Reporting Groups
  Description
Arm 1 (Pac --> ddAC)

Patients receive paclitaxel (pac) IV over 60 minutes once weekly in weeks 1-12. Patients then receive dose-dense doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 5-30 minutes (ddAC) once in weeks 13, 15, 17, and 19.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

Arm 2 (Pac + Bev --> ddAC + Bev)

Patients receive pac and ddAC as in arm 1. Patients also receive bevacizumab (bev) IV over 30-90 minutes in weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

bevacizumab: Given IV

Arm 3 (Pac + Carboplatin --> ddAC)

Patients receive pac and ddAC as in arm 1. Patients also receive carboplatin IV over 30 minutes once in weeks 1, 4, 7, and 10.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

carboplatin: Given IV

Arm 4 (Pac + Carboplatin + Bev --> ddAC + Bev)

Patients receive pac and ddAC as in arm 1, bev as in arm 2, and carboplatin as in arm 3.

doxorubicin hydrochloride: Given IV

paclitaxel: Given IV

cyclophosphamide: Given IV

bevacizumab: Given IV

carboplatin: Given IV

Total Total of all reporting groups

Baseline Measures
    Arm 1 (Pac --> ddAC)     Arm 2 (Pac + Bev --> ddAC + Bev)     Arm 3 (Pac + Carboplatin --> ddAC)     Arm 4 (Pac + Carboplatin + Bev --> ddAC + Bev)     Total  
Number of Participants  
[units: participants]
  115     113     113     113     454  
Age  
[units: years]
Mean (Standard Deviation)
  50.2  (11.1)     48.3  (10.8)     50.9  (10.8)     47.1  (9.8)     49.1  (10.7)  
Gender  
[units: participants]
         
Female     115     113     113     113     454  
Male     0     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
         
American Indian or Alaska Native     1     0     0     2     3  
Asian     1     5     4     3     13  
Native Hawaiian or Other Pacific Islander     1     0     0     0     1  
Black or African American     20     21     27     21     89  
White     86     84     80     81     331  
More than one race     1     1     1     2     5  
Unknown or Not Reported     5     2     1     4     12  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Pathologic Complete Response (pCR) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is).   [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ]

2.  Primary:   Pathologic Complete Response (pCR) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is).   [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ]

3.  Secondary:   Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0).   [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ]

4.  Secondary:   Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0).   [ Time Frame: At the time of definitive surgical removal, up to 28 weeks ]

5.  Secondary:   Incidence and Severity of Post-op Complications, Namely Excessive Bleeding, Delayed Wound Healing, and Wound Dehiscence.   [ Time Frame: at definitive surgery, up to 28 weeks ]

6.  Secondary:   Pathologic Stage in the Breast and in the Breast Plus Axilla as Measured by American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) Staging Criteria (Version 6)   [ Time Frame: at definitive surgery, up to 28 weeks ]
Results not yet reported.   Anticipated Reporting Date:   10/2018   Safety Issue:   No

7.  Secondary:   Radiographic Response Assessed by Tumor Measurement   [ Time Frame: Baseline; at completion of neoadjuvant therapy ]
Results not yet reported.   Anticipated Reporting Date:   10/2018   Safety Issue:   No

8.  Secondary:   Clinical Response Assessed by Tumor Measurement   [ Time Frame: Baseline; at completion of neoadjuvant therapy ]
Results not yet reported.   Anticipated Reporting Date:   10/2018   Safety Issue:   No

9.  Secondary:   Overall Survival   [ Time Frame: up to 10 years ]
Results not yet reported.   Anticipated Reporting Date:   10/2018   Safety Issue:   No

10.  Secondary:   Recurrence-free Survival   [ Time Frame: up to 10 years ]
Results not yet reported.   Anticipated Reporting Date:   10/2018   Safety Issue:   No

11.  Secondary:   Time to First Failure, Defined as First Instance of Ipsilateral Invasive Breast Tumor Recurrence, Local/Regional Invasive Breast Cancer Recurrence, Distant Recurrence, or Death From Any Cause   [ Time Frame: up to 10 years ]
Results not yet reported.   Anticipated Reporting Date:   10/2018   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: William M. Sikov, M.D.
Organization: Warren Alpert Medical School of Brown University, Department of Medicine
phone: 401-793-7151
e-mail: wsikov@lifespan.org


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00861705     History of Changes
Other Study ID Numbers: NCI-2009-01172
NCI-2009-01172 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CALGB-40603
CALGB 40603/CTSU 40603
CDR0000636850
CALGB 40603 ( Other Identifier: Alliance for Clinical Trials in Oncology )
CALGB-40603 ( Other Identifier: CTEP )
U10CA180821 ( US NIH Grant/Contract Award Number )
U10CA031946 ( US NIH Grant/Contract Award Number )
Study First Received: March 12, 2009
Results First Received: January 12, 2015
Last Updated: September 28, 2015
Health Authority: United States: Food and Drug Administration